Wasana Stitchantrakul - Academia.edu (original) (raw)
Papers by Wasana Stitchantrakul
The Journal of Urology, May 1, 2006
It has been speculated that calcium supplement in subjects with low oxalate intake might increase... more It has been speculated that calcium supplement in subjects with low oxalate intake might increase the risk of calcium stone formation due to an increase in calcium absorption without a significant reduction in oxalate absorption. There have been no human studies addressing specifically the effects of taking calcium supplements in populations whose dietary oxalate is low. This study was conducted to determine the effects of calcium supplements on the risk of calcium stone formation in a population with low oxalate intake. Thirty-two healthy male navy privates, 22.7±1.9 (mean ± SD) years old, who had oxalate intake of less than 1 mmol/day, a serum creatinine of less than 150 µmol/l, and no history of renal stones, participated in the study. Dietary oxalate was controlled to be under 1 mmol/day throughout the study. Twenty-four hour urine collections for the determination of urinary constituents were obtained at baseline and after taking calcium supplements. Detection of calcium oxalate was performed to assess the risk of calcium oxalate stone formation. The urinary excretion of calcium was significantly elevated above baseline values while taking the calcium supplements (3.48±2.13 vs 5.17±2.61 mmol/d, p < 0.05) and urinary oxalate was significantly decreased when the subjects took calcium supplements compared to the corresponding baseline value (0.13±0.05 vs 0.17±0.07 mmol/d, p = 0.01). Urinary citrate was significantly elevated when the subjects took calcium supplements compared to the baseline (0.83±0.57 vs 0.64±0.39 mmol/d, p = 0.03). There was no significant alteration in the activity products of calcium oxalate while taking the calcium supplements (0.54±0.25 vs 0.57±0.22, p = 0.54). The effect of calcium supplements with meals, for the reduction of the risk of calcium stone formation, was unchanged, even in a population whose oxalate intake is rather low. Taking calcium supplements resulted in a reduction in urinary oxalates and an elevation in urinary citrates. Both alterations in urinary constituents counterbalanced the elevation in urinary calcium which resulted from the calcium supplements.
Annals of Translational Medicine, Sep 1, 2017
BackgroundCancer is a chronic disease and currently the leading cause of death in Thailand. Funct... more BackgroundCancer is a chronic disease and currently the leading cause of death in Thailand. Functional defect of DNA repair pathway in cells plays role carcinogenesis. Conversely, cancer cells also remain the trace DNA repair pathway to survive under the genotoxic environment, i.e., chemotherapy, and result in resistance to the treatment. Previous reports have shown that DNA repair targeted therapy could improve the conventional treatment. The Ring Finger E3 ubiquitin ligase gene (RNF43) is of interest because the function in tumorigenesis related to DNA repair mechanism is ambiguous. Ubiquitin post-translational modification involves in many cellular processes, such as proteasomal degradation and DNA repair regulation. A number of studies indicated contribution of RNF43 toward proteasomal degradation of Frizzled receptor that is related to carcinogenesis. However, there has been no study investigating molecular mechanism of RNF43 on the DNA repair process which could participate in cancer.MethodsThe aim of this study was to investigate the functional role of RNF43 in DNA repair pathways that related to carcinogenesis. DT40 and related knockout strains were used as the model to study the function of RNF43. We first generated complete knockout cell line [DT40-RNF43(-/-)], and the abolition of RNF43 mRNA level was confirmed by qRT-PCR.ResultsGrowth curve analysis revealed that DT40-RNF43(-/-) was comparable to the wild-type. The preliminary results of colony formation assay with the genotoxic compounds revealed that RNF43 might have a role in DNA double-strand break (DSB) repair pathways.ConclusionsFurther molecular study on RNF43 binding partner in response to DNA damage repair pathway would facilitate the understanding of RNF43 contribution in DNA-repair related carcinogenesis and provide a new target for personalized medicine in the future.
Genes to Cells, Oct 19, 2020
Ring finger protein 43 (RNF43) is an E3 ubiquitin ligase which is well‐known for its role in nega... more Ring finger protein 43 (RNF43) is an E3 ubiquitin ligase which is well‐known for its role in negative regulation of the Wnt‐signaling pathway. However, the function in DNA double‐strand break repairs has not been investigated. In this study, we used a lymphoblast cell line, DT40, and mouse embryonic fibroblast as cellular models to study DNA double‐strand break (DSB) repairs. For this purpose, we created RNF43 knockout, RNF43−/− DT40 cell line to investigate DSB repairs. We found that deletion of RNF43 does not interfere with cell proliferation. However, after exposure to various types of DNA‐damaging agents, RNF43−/− cells become more sensitive to topoisomerase II inhibitors, etoposide, and ICRF193, than wild type cells. Our results also showed that depletion of RNF43 results in apoptosis upon etoposide‐mediated DNA damage. The delay in resolution of γH2AX and 53BP1 foci formation after etoposide treatment, as well as epistasis analysis with DNAPKcs, suggested that RNF43 might participate in DNA repair of etoposide‐induced DSB via non‐homologous end joining. Disturbed γH2AX foci formation in MEFs following pulse etoposide treatment supported the notion that RNF43 also functions DNA repair in mammalian cells. These findings propose two possible functions of RNF43, either participating in NHEJ or removing the blockage of 5′ topo II adducts from DSB ends.
PubMed, Aug 1, 2010
Objective: To evaluate 25 hydroxyvitamin D (25-OH-D) deficiency in a cohort ofpredialysis CKD pat... more Objective: To evaluate 25 hydroxyvitamin D (25-OH-D) deficiency in a cohort ofpredialysis CKD patients and the treatment effect and safety of high dose ergocalciferol supplement in predialysis CKD. Material and method: Fifty-six predialysis CKD patients who came for a regular visit at a single hospital with calculated glomerular filtration rate < or =60 mL/min/1.73 m2 were screened for 25-OH-D levels. Forty-four patients with 25-OH-D deficiency were recruited into this prospective observational study that examined the effect of high dose oral ergocalciferol supplementation. After eight weeks, 37 patients completed the follow-up and biochemical parameters were reevaluated and analyzed. Results: The mean 25-OH-D level of 56 patients was 25.6 +/- 8 ng/mL. Forty-four (78.5%) patients had 25-OH-D levels less than 30 ng/mL and four (7.1%) had severe deficiency with the level less than 15 ng/mL. High dose ergocalciferol supplement successively increased 25-OH-D levels in 35 (95%) patients. 25-OH-D levels increased significantly from 22 +/- 4.8 to 34.5 +/- 10.8 ng/mL after eight weeks (p < 0.001). During the study period, there were no changes in serum calcium, phosphate, and PTH. There was no other side effect associated with the treatment. Conclusion: 25-OH-D deficiency were found in this cohort of predialysis CKD patients. Ergocalciferol was a safe and effective supplement for the 25-OH-D in predialysis CKD.
Experimental and Clinical Endocrinology & Diabetes, May 15, 2009
Chronic metabolic acidosis (CMA) is known to induce renal phosphate wasting and hypophosphatemia ... more Chronic metabolic acidosis (CMA) is known to induce renal phosphate wasting and hypophosphatemia by enhancing bone resorption and inhibiting renal phosphate reabsorption. However, nothing is known regarding changes in the plasma levels of phosphate-regulating hormones during CMA, especially in humans with normal kidney function. Fifteen healthy Thai female volunteers were given NH (4)Cl orally for 7 days to induce CMA with or without oral phosphate supplementation. Blood and 24-h urine specimens were collected prior to and after CMA induction. Plasma concentrations and fractional excretion of calcium and inorganic phosphate as well as plasma levels of fibroblast growth factor (FGF) 23, 25(OH)D (3), 1,25(OH) (2)D (3) and intact parathyroid hormone (iPTH) were determined. CMA led to hypophosphatemia and hypocalcemia with increases in the fractional excretion of calcium and phosphate. Plasma concentrations of FGF23, 25(OH)D (3) and iPTH were decreased, whereas that of 1,25(OH) (2)D (3) was increased. After oral phosphate supplementation, CMA-induced changes in the concentrations of the studied ions, FGF23 and 25(OH)D (3), but not those of 1,25(OH) (2)D (3) and iPTH, were diminished. The CMA-induced hypophosphatemia was likely to initiate a negative feedback response, thereby leading to reduction in the plasma levels of hyperphosphaturic hormones, FGF23 and PTH. An increase in the plasma 1,25(OH) (2)D (3) level, despite diminishing 25(OH)D (3) storage pool, may help enhance the intestinal phosphate absorption. Oral phosphate supplementation abolished the effects of CMA on FGF23 and 25(OH)D (3) levels, suggesting that the plasma phosphate concentration is the primary regulator of the plasma levels of these hormones during CMA.
Neurological Sciences, Apr 19, 2019
Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children... more Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern. Considering the high prevalence of SMA carrier in many population, it is possible that SMA is one of the most common autosomal recessive disorders in Thailand and Southeast Asia. In this study, we analyzed DNA from peripheral blood of 505 healthy Thai adults using quantitative PCR-based for SMN1 gene exon 7 copy number analysis. Individual samples with heterozygous deletion of SMN1 gene were confirmed with MLPA. The result identified 9 samples (1.78%) with heterozygous deletion and 39 samples as more than 2 copies of SMN1. No homozygous deletion was detected in the samples. In conclusion, we established carrier frequency of SMA in selected Thai population at 1.8% from 505 participants. The prevalence coincides with prevalence in East Asia and Caucasian population. The result could be implemented for SMA carrier screening in couples at risk in the region.
Kidney International, Feb 1, 2007
Nephrology Dialysis Transplantation, Jul 12, 2010
Background. Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as end... more Background. Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as endocrine function. Adipose tissue communicates with the rest of the body through synthesis and release adipokines, such as leptin, adiponectin and TNF-alpha. Adiponectin enhances insulin sensitivity and possesses anti-atherogenic and anti-inflammatory properties. Circulating adiponectin correlates inversely with cardiovascular events. It is possible that MA negatively regulates adiponectin contributing to poor patient outcome. The present study investigates the effect of MA on adiponectin in vivo and in vitro. Methods. Twenty healthy female volunteers underwent a 7-day course of oral ammonium chloride (NH 4 Cl)-induced acidosis. Serum adiponectin was determined before and after NH 4 Cl ingestion. Adipocytes were differentiated from their precursors, human mesenchymal stem cells (hMSCs), in culture. Concentrated HCl was added to the media to lower pH. Adiponectin mRNA and protein were determined at 48 and 96 h by real-time RT-PCR and ELISA, respectively. Results. After a 7-day course of NH 4 Cl, serum bicarbonate decreased significantly associated with the increase in urine ammonium and titratable acid. Adiponectin decreased significantly from 10 623 to 9723 pg/mL (P < 0.005). MA suppressed adiponectin mRNA in hMSC-derived adipocytes at 48 and 96 h (P < 0.01). The amount of adiponectin released into the culture media declined corresponding to the mRNA levels (P < 0.001). MA did not affect adipocyte triglyceride or protein content. Conclusions. MA lowered circulating adiponectin through inhibition of adiponectin gene transcription in adipocytes.
Journal of The American Society of Nephrology, Mar 1, 2005
End-stage kidney disease has become an increasing burden in all regions of the world. However, li... more End-stage kidney disease has become an increasing burden in all regions of the world. However, limited epidemiologic data on chronic kidney disease in Southeast Asian populations are available. Therefore, a cohort study over a period of 12 yr (1985 to 1997) in 3499 employees of the Electric Generation Authority of Thailand, aged 35 to 55 yr, was conducted to determine the prevalence of decreased kidney function and risk factors associated with future development of decreased kidney function. The prevalence of decreased kidney function (GFR <60 ml/min) increased from 1.7% (95% confidence interval [CI], 1.3 to 2.1) in 1985 to 6.8% (95% CI, 5.7 to 7.9) in 1997, and the prevalence of elevated serum creatinine was 6.1% (95% CI, 5.3 to 6.9) and 16.9% (95% CI, 15.3 to 18.5) in 1985 and 1997 surveys, respectively. The adjusted odds ratio for future development of decreased kidney function was 2.57 (1.0 to 6.81) for systolic hypertension (>159 mmHg), 1.82 (1.12 to 2.98) for hyperuricemia (>6.29 mg/dl), 1.68 (1.02 to 2.77) for elevated body mass index (>24.9 kg/m 2) compared with subjects with systolic BP <140 mmHg, serum uric acid <4.5 mg/dl, and body mass index 20.8 to 22.8 kg/m 2. The rising prevalence of decreased kidney function in this population resulted mainly from the increasing prevalence of the risk factors in the population. Screening to detect decreased kidney function and early intervention to modify the associated risk factors should be considered in otherwise healthy individuals. Future studies are also necessary to determine whether implementation of these measures results in a reduction of ESRD incidence in the population.
Kidney International, Dec 1, 2002
Conclusions. This study demonstrates that alkaline therapy Bone histology and bone mineral densit... more Conclusions. This study demonstrates that alkaline therapy Bone histology and bone mineral density after correction of corrects abnormal bone cell function and elevates bone mineral acidosis in distal renal tubular acidosis. density in dRTA patients, indicating the causal role of acidosis Background. The association between chronic metabolic acin the alterations of bone cell functions and reduction in bone idosis and alterations in bone cell functions has been demonmineral density. Parathyroid gland activity also may be involved strated in vitro and in animal studies. However, the causal role in the adaptation of the body to chronic metabolic acidosis. of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density Distal renal tubular acidosis (dRTA) is a condition and bone histology before and after correction of acidosis among associated with impaired renal acid excretion, resulting patients with distal renal tubular acidosis (dRTA) in accumulation of acid in the body. The disease is associ-Methods. Correction of metabolic acidosis by potassium ciated with growth retardation [1], skeletal pain, abnormal trate was done in non-azotemic dRTA patients, 6 females and bone metabolism, and pathologic fractures [2, 3]. Our 4 males, who had never received long-term alkaline therapy previous study on bone mineral metabolism in patients before enrolling into this study. Blood chemistries, serum intact with dRTA demonstrated significant suppression in both parathyroid hormone, and 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, potassium, bone formation and bone resorption in association with bone mineral density determination, and transiliac bone biopsy mild elevation in osteoid volume [3]. Most dRTA patients were done in all patients at baseline and after one year of also had a marked reduction in bone mineral density of potassium citrate therapy. spine and hip [3]. A putative causal role of metabolic Results. Significant elevations in serum bicarbonate (16.5 Ϯ acidosis in the development of skeletal growth retardation 3.0 vs. 24.6 Ϯ 2.8 mEq/L, P Ͻ 0.05) and urinary potassium is supported by the fact that alkaline therapy normalized excretion (35.2 Ϯ 7.9 vs. 55.4 Ϯ3.5 mEq/L, P Ͻ 0.05) were observed after potassium citrate therapy. No significant alter
Journal of Bone and Mineral Research, Sep 1, 2003
This study demonstrated that there was extensive iron staining on trabecular surface and marked r... more This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF‐I was reduced and may modulate the reduction of bone mass.Introduction: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited. Therefore, this study was systematically conducted to determine the alterations in thalassemia patients.Methods: Serum biochemical parameters, trans‐iliac crest bone biopsy, and determination of bone mineral density of femur and lumbar spine were done in 18 thalassemic patients (10 females and 8 males).Results: Serum osteocalcin, carboxy terminal teleopeptide fragment of type I collagen, and parathyroid hormone levels were within normal limits, but serum 25(OH) vitamin D (19.3 ± 1.6 ng/ml) and 1,25(OH)2 vitamin D (33.77 ± 1.51 pg/ml) levels were decreased. Serum insulin‐like growth factor I (IGF‐I; 145.2 ± 20 ng/ml) was suppressed, whereas serum ferritin (1366.6 ± 253.9 ng/ml) was markedly elevated. Reduced bone mineral density was found in all studied areas. Trabecular bone volume was significantly decreased (16.65 ± 1.12%), whereas bone formation rate, eroded surface, and other bone histomorphometric parameters were within normal limits. The trabecular bone volume varied significantly with bone mineral density of total femur (r = 0.48, p = 0.04). There was an extensive stainable iron surface on the mineral front (9–60%). Significant correlation between serum IGF‐I, serum ferritin, stainable iron surface, and bone mineral density, lumbar spine, and total femur were found. Serum IGF‐I correlated with trabecular bone volume (r = 0.6, p = 0.03), inversely with both serum ferritin level (r = −0.6, p < 0.01), and inversely with stainable iron surface (r = −0.53, p = 0.02). Multiple regression analysis demonstrated that IGF‐I was the only independent variable that determined bone mineral density of lumbar spine and total femur.Conclusion: Low bone mineral density and reduced trabecular bone volume with extensive iron deposition are the predominant findings in thalassemic patients. There was no evidence of increased bone resorption or mineralization defect. A reduction in circulatory IGF‐I may modulate the reduction of bone mass.
Revista del climaterio, 2003
Kidney International, Mar 1, 2001
regarding bone densitometric measurement in distal RTA has been published. Previous in vitro stud... more regarding bone densitometric measurement in distal RTA has been published. Previous in vitro studies sug
acidosis lowers circulating adiponectin through inhibition of adiponectin gene transcription
日本人類遺伝学会大会プログラム・抄録集, 2016
BMC Complementary and Alternative Medicine, Sep 23, 2015
Background: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented d... more Background: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis. Methods: A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated. Results: A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7 %) and 9/28 (32.1 %) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027). Conclusions: Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study [Clinicaltrials.Gov Identifier Nct01800487].
BioMed Research International, Feb 6, 2023
The inhibition of poly(ADP-ribose) polymerases (PARPs) and ataxia telangiectasia and Rad3-related... more The inhibition of poly(ADP-ribose) polymerases (PARPs) and ataxia telangiectasia and Rad3-related (ATR) would be an alternative approach for cancer treatments. The aim of this study is to investigate the synergy of the different combinations of PARP inhibitors (olaparib, talazoparib, or veliparib) and ATR inhibitor AZD6738. A drug combinational synergy screen that combines olaparib, talazoparib, or veliparib with AZD6738 was performed to identify the synergistic interaction, and the combination index was calculated to verify synergy. TK6 isogenic cell lines with defects in different DNA repair genes were used as a model. Cell cycle analysis, micronucleus induction, and focus formation assays of serine-139 phosphorylation of the histone variant H2AX demonstrated that AZD6738 diminished G2/M checkpoint activation induced by PARP inhibitors and allowed DNA damage-containing cells to continue dividing, leading to greater increases in micronuclei as well as doublestrand DNA breaks in mitotic cells. We also found that AZD6738 was likely to potentiate cytotoxicity of PARP inhibitors in homologous recombination repair deficiency cell lines. AZD6738 sensitized more genotypes of DNA repair-deficient cell lines to talazoparib than to olaparib and veliparib, respectively. The combinational approach of PARP and ATR inhibition to enhance response to PARP inhibitors could expand the utility of PARP inhibitors to cancer patients without BRCA1/2 mutations.
Annals of Translational Medicine, Sep 1, 2017
BackgroundCytotoxic chemotherapy and/or radiation therapy inducing DNA damage is a part of cancer... more BackgroundCytotoxic chemotherapy and/or radiation therapy inducing DNA damage is a part of cancer treatment. Tripartite motif 29 (TRIM29) is highly expressed in many malignancies; for example, pancreatic cancer which is notorious resistant to cytotoxic chemotherapy and radiation therapy. TRIM29 is a member of the TRIM protein family composed of more than 70 members associated with a broad of biological processes. Originally, TRIM29 gene was described as a candidate gene responsible for ataxia- telangiectasia (AT); however, TRIM29 was dismissed as AT-causing gene after ataxia- telangiectasia mutated (ATM) was discovered as a causative gene for AT. A few studies about TRIM29 suggested that it was involved in DNA damage response and high expression of TRIM29 promoted resistance to ionizing radiation (IR), which induces DNA double strand breaks (DSB). Nevertheless, the functions of TRIM29 in DNA damage responses and/or DNA repair mechanisms are still unclear.MethodsTo investigate the functions of TRIM29 in DNA repair mechanisms, wild-type DT40 (WT) and mutant strains have been selected and used as a model. Firstly, the researchers generated the TRIM29 knockout (TRIM29-/-/-/+).ResultsThe growth analysis showed that TRIM29-/-/-/+ was comparable to WT. The results of DNA-damaging agent sensitivity using clonogenic survival assays indicated that TRIM29-/-/-/+ clones displayed increased sensitivity to topoisomerase 2 inhibitors which induce DNA DSBs repaired by non-homologous end joining (NHEJ) pathway. The TRIM29-/-/-/+ clones also exhibited mild sensitivity to camptothecin and cisplatin, indicating that TRIM29 plays a role in DNA DSB repair mechanisms.ConclusionsFurther study of TRIM29 in response to DNA DSBs may help improve the understanding of functions of TRIM29. In the future, TRIM29 might be a target for anti-cancer drug, leading to improvement of cancer treatment effectiveness.
PubMed, 2023
Cancer is the leading cause of death worldwide, resulting in the mortality of more than 10 millio... more Cancer is the leading cause of death worldwide, resulting in the mortality of more than 10 million people in 2020, according to Global Cancer Statistics 2020. A potential cancer therapy involves targeting the DNA repair process by inhibiting PARP-1. In this study, classification models were constructed using a non-redundant set of 2018 PARP-1 inhibitors. Briefly, compounds were described by 12 fingerprint types and built using the random forest algorithm concomitant with various sampling approaches. Results indicated that PubChem with an oversampling approach yielded the best performance, with a Matthews correlation coefficient > 0.7 while also affording interpretable molecular features. Moreover, feature importance, as determined from the Gini index, revealed that the aromatic/cyclic/heterocyclic moiety, nitrogen-containing fingerprints, and the ether/aldehyde/alcohol moiety were important for PARP-1 inhibition. Finally, our predictive model was deployed as a web application called PARP1pred and is publicly available at https://parp1pred.streamlitapp.com, allowing users to predict the biological activity of query compounds using their SMILES notation as the input. It is anticipated that the model described herein will aid in the discovery of effective PARP-1 inhibitors.
FEBS Open Bio, Aug 31, 2020
ɣ-H2AX phosphorylated H2A histone family member X 53BP1 tumor suppressor p53-binding protein 1 al... more ɣ-H2AX phosphorylated H2A histone family member X 53BP1 tumor suppressor p53-binding protein 1 alt-EJ alternative end joining ATDC ataxia telangiectasia group D complementing protein ATM ataxia telangiectasia mutated BASC BRCA1-associated surveillance complex
The Journal of Urology, May 1, 2006
It has been speculated that calcium supplement in subjects with low oxalate intake might increase... more It has been speculated that calcium supplement in subjects with low oxalate intake might increase the risk of calcium stone formation due to an increase in calcium absorption without a significant reduction in oxalate absorption. There have been no human studies addressing specifically the effects of taking calcium supplements in populations whose dietary oxalate is low. This study was conducted to determine the effects of calcium supplements on the risk of calcium stone formation in a population with low oxalate intake. Thirty-two healthy male navy privates, 22.7±1.9 (mean ± SD) years old, who had oxalate intake of less than 1 mmol/day, a serum creatinine of less than 150 µmol/l, and no history of renal stones, participated in the study. Dietary oxalate was controlled to be under 1 mmol/day throughout the study. Twenty-four hour urine collections for the determination of urinary constituents were obtained at baseline and after taking calcium supplements. Detection of calcium oxalate was performed to assess the risk of calcium oxalate stone formation. The urinary excretion of calcium was significantly elevated above baseline values while taking the calcium supplements (3.48±2.13 vs 5.17±2.61 mmol/d, p < 0.05) and urinary oxalate was significantly decreased when the subjects took calcium supplements compared to the corresponding baseline value (0.13±0.05 vs 0.17±0.07 mmol/d, p = 0.01). Urinary citrate was significantly elevated when the subjects took calcium supplements compared to the baseline (0.83±0.57 vs 0.64±0.39 mmol/d, p = 0.03). There was no significant alteration in the activity products of calcium oxalate while taking the calcium supplements (0.54±0.25 vs 0.57±0.22, p = 0.54). The effect of calcium supplements with meals, for the reduction of the risk of calcium stone formation, was unchanged, even in a population whose oxalate intake is rather low. Taking calcium supplements resulted in a reduction in urinary oxalates and an elevation in urinary citrates. Both alterations in urinary constituents counterbalanced the elevation in urinary calcium which resulted from the calcium supplements.
Annals of Translational Medicine, Sep 1, 2017
BackgroundCancer is a chronic disease and currently the leading cause of death in Thailand. Funct... more BackgroundCancer is a chronic disease and currently the leading cause of death in Thailand. Functional defect of DNA repair pathway in cells plays role carcinogenesis. Conversely, cancer cells also remain the trace DNA repair pathway to survive under the genotoxic environment, i.e., chemotherapy, and result in resistance to the treatment. Previous reports have shown that DNA repair targeted therapy could improve the conventional treatment. The Ring Finger E3 ubiquitin ligase gene (RNF43) is of interest because the function in tumorigenesis related to DNA repair mechanism is ambiguous. Ubiquitin post-translational modification involves in many cellular processes, such as proteasomal degradation and DNA repair regulation. A number of studies indicated contribution of RNF43 toward proteasomal degradation of Frizzled receptor that is related to carcinogenesis. However, there has been no study investigating molecular mechanism of RNF43 on the DNA repair process which could participate in cancer.MethodsThe aim of this study was to investigate the functional role of RNF43 in DNA repair pathways that related to carcinogenesis. DT40 and related knockout strains were used as the model to study the function of RNF43. We first generated complete knockout cell line [DT40-RNF43(-/-)], and the abolition of RNF43 mRNA level was confirmed by qRT-PCR.ResultsGrowth curve analysis revealed that DT40-RNF43(-/-) was comparable to the wild-type. The preliminary results of colony formation assay with the genotoxic compounds revealed that RNF43 might have a role in DNA double-strand break (DSB) repair pathways.ConclusionsFurther molecular study on RNF43 binding partner in response to DNA damage repair pathway would facilitate the understanding of RNF43 contribution in DNA-repair related carcinogenesis and provide a new target for personalized medicine in the future.
Genes to Cells, Oct 19, 2020
Ring finger protein 43 (RNF43) is an E3 ubiquitin ligase which is well‐known for its role in nega... more Ring finger protein 43 (RNF43) is an E3 ubiquitin ligase which is well‐known for its role in negative regulation of the Wnt‐signaling pathway. However, the function in DNA double‐strand break repairs has not been investigated. In this study, we used a lymphoblast cell line, DT40, and mouse embryonic fibroblast as cellular models to study DNA double‐strand break (DSB) repairs. For this purpose, we created RNF43 knockout, RNF43−/− DT40 cell line to investigate DSB repairs. We found that deletion of RNF43 does not interfere with cell proliferation. However, after exposure to various types of DNA‐damaging agents, RNF43−/− cells become more sensitive to topoisomerase II inhibitors, etoposide, and ICRF193, than wild type cells. Our results also showed that depletion of RNF43 results in apoptosis upon etoposide‐mediated DNA damage. The delay in resolution of γH2AX and 53BP1 foci formation after etoposide treatment, as well as epistasis analysis with DNAPKcs, suggested that RNF43 might participate in DNA repair of etoposide‐induced DSB via non‐homologous end joining. Disturbed γH2AX foci formation in MEFs following pulse etoposide treatment supported the notion that RNF43 also functions DNA repair in mammalian cells. These findings propose two possible functions of RNF43, either participating in NHEJ or removing the blockage of 5′ topo II adducts from DSB ends.
PubMed, Aug 1, 2010
Objective: To evaluate 25 hydroxyvitamin D (25-OH-D) deficiency in a cohort ofpredialysis CKD pat... more Objective: To evaluate 25 hydroxyvitamin D (25-OH-D) deficiency in a cohort ofpredialysis CKD patients and the treatment effect and safety of high dose ergocalciferol supplement in predialysis CKD. Material and method: Fifty-six predialysis CKD patients who came for a regular visit at a single hospital with calculated glomerular filtration rate < or =60 mL/min/1.73 m2 were screened for 25-OH-D levels. Forty-four patients with 25-OH-D deficiency were recruited into this prospective observational study that examined the effect of high dose oral ergocalciferol supplementation. After eight weeks, 37 patients completed the follow-up and biochemical parameters were reevaluated and analyzed. Results: The mean 25-OH-D level of 56 patients was 25.6 +/- 8 ng/mL. Forty-four (78.5%) patients had 25-OH-D levels less than 30 ng/mL and four (7.1%) had severe deficiency with the level less than 15 ng/mL. High dose ergocalciferol supplement successively increased 25-OH-D levels in 35 (95%) patients. 25-OH-D levels increased significantly from 22 +/- 4.8 to 34.5 +/- 10.8 ng/mL after eight weeks (p < 0.001). During the study period, there were no changes in serum calcium, phosphate, and PTH. There was no other side effect associated with the treatment. Conclusion: 25-OH-D deficiency were found in this cohort of predialysis CKD patients. Ergocalciferol was a safe and effective supplement for the 25-OH-D in predialysis CKD.
Experimental and Clinical Endocrinology & Diabetes, May 15, 2009
Chronic metabolic acidosis (CMA) is known to induce renal phosphate wasting and hypophosphatemia ... more Chronic metabolic acidosis (CMA) is known to induce renal phosphate wasting and hypophosphatemia by enhancing bone resorption and inhibiting renal phosphate reabsorption. However, nothing is known regarding changes in the plasma levels of phosphate-regulating hormones during CMA, especially in humans with normal kidney function. Fifteen healthy Thai female volunteers were given NH (4)Cl orally for 7 days to induce CMA with or without oral phosphate supplementation. Blood and 24-h urine specimens were collected prior to and after CMA induction. Plasma concentrations and fractional excretion of calcium and inorganic phosphate as well as plasma levels of fibroblast growth factor (FGF) 23, 25(OH)D (3), 1,25(OH) (2)D (3) and intact parathyroid hormone (iPTH) were determined. CMA led to hypophosphatemia and hypocalcemia with increases in the fractional excretion of calcium and phosphate. Plasma concentrations of FGF23, 25(OH)D (3) and iPTH were decreased, whereas that of 1,25(OH) (2)D (3) was increased. After oral phosphate supplementation, CMA-induced changes in the concentrations of the studied ions, FGF23 and 25(OH)D (3), but not those of 1,25(OH) (2)D (3) and iPTH, were diminished. The CMA-induced hypophosphatemia was likely to initiate a negative feedback response, thereby leading to reduction in the plasma levels of hyperphosphaturic hormones, FGF23 and PTH. An increase in the plasma 1,25(OH) (2)D (3) level, despite diminishing 25(OH)D (3) storage pool, may help enhance the intestinal phosphate absorption. Oral phosphate supplementation abolished the effects of CMA on FGF23 and 25(OH)D (3) levels, suggesting that the plasma phosphate concentration is the primary regulator of the plasma levels of these hormones during CMA.
Neurological Sciences, Apr 19, 2019
Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children... more Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern. Considering the high prevalence of SMA carrier in many population, it is possible that SMA is one of the most common autosomal recessive disorders in Thailand and Southeast Asia. In this study, we analyzed DNA from peripheral blood of 505 healthy Thai adults using quantitative PCR-based for SMN1 gene exon 7 copy number analysis. Individual samples with heterozygous deletion of SMN1 gene were confirmed with MLPA. The result identified 9 samples (1.78%) with heterozygous deletion and 39 samples as more than 2 copies of SMN1. No homozygous deletion was detected in the samples. In conclusion, we established carrier frequency of SMA in selected Thai population at 1.8% from 505 participants. The prevalence coincides with prevalence in East Asia and Caucasian population. The result could be implemented for SMA carrier screening in couples at risk in the region.
Kidney International, Feb 1, 2007
Nephrology Dialysis Transplantation, Jul 12, 2010
Background. Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as end... more Background. Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as endocrine function. Adipose tissue communicates with the rest of the body through synthesis and release adipokines, such as leptin, adiponectin and TNF-alpha. Adiponectin enhances insulin sensitivity and possesses anti-atherogenic and anti-inflammatory properties. Circulating adiponectin correlates inversely with cardiovascular events. It is possible that MA negatively regulates adiponectin contributing to poor patient outcome. The present study investigates the effect of MA on adiponectin in vivo and in vitro. Methods. Twenty healthy female volunteers underwent a 7-day course of oral ammonium chloride (NH 4 Cl)-induced acidosis. Serum adiponectin was determined before and after NH 4 Cl ingestion. Adipocytes were differentiated from their precursors, human mesenchymal stem cells (hMSCs), in culture. Concentrated HCl was added to the media to lower pH. Adiponectin mRNA and protein were determined at 48 and 96 h by real-time RT-PCR and ELISA, respectively. Results. After a 7-day course of NH 4 Cl, serum bicarbonate decreased significantly associated with the increase in urine ammonium and titratable acid. Adiponectin decreased significantly from 10 623 to 9723 pg/mL (P < 0.005). MA suppressed adiponectin mRNA in hMSC-derived adipocytes at 48 and 96 h (P < 0.01). The amount of adiponectin released into the culture media declined corresponding to the mRNA levels (P < 0.001). MA did not affect adipocyte triglyceride or protein content. Conclusions. MA lowered circulating adiponectin through inhibition of adiponectin gene transcription in adipocytes.
Journal of The American Society of Nephrology, Mar 1, 2005
End-stage kidney disease has become an increasing burden in all regions of the world. However, li... more End-stage kidney disease has become an increasing burden in all regions of the world. However, limited epidemiologic data on chronic kidney disease in Southeast Asian populations are available. Therefore, a cohort study over a period of 12 yr (1985 to 1997) in 3499 employees of the Electric Generation Authority of Thailand, aged 35 to 55 yr, was conducted to determine the prevalence of decreased kidney function and risk factors associated with future development of decreased kidney function. The prevalence of decreased kidney function (GFR <60 ml/min) increased from 1.7% (95% confidence interval [CI], 1.3 to 2.1) in 1985 to 6.8% (95% CI, 5.7 to 7.9) in 1997, and the prevalence of elevated serum creatinine was 6.1% (95% CI, 5.3 to 6.9) and 16.9% (95% CI, 15.3 to 18.5) in 1985 and 1997 surveys, respectively. The adjusted odds ratio for future development of decreased kidney function was 2.57 (1.0 to 6.81) for systolic hypertension (>159 mmHg), 1.82 (1.12 to 2.98) for hyperuricemia (>6.29 mg/dl), 1.68 (1.02 to 2.77) for elevated body mass index (>24.9 kg/m 2) compared with subjects with systolic BP <140 mmHg, serum uric acid <4.5 mg/dl, and body mass index 20.8 to 22.8 kg/m 2. The rising prevalence of decreased kidney function in this population resulted mainly from the increasing prevalence of the risk factors in the population. Screening to detect decreased kidney function and early intervention to modify the associated risk factors should be considered in otherwise healthy individuals. Future studies are also necessary to determine whether implementation of these measures results in a reduction of ESRD incidence in the population.
Kidney International, Dec 1, 2002
Conclusions. This study demonstrates that alkaline therapy Bone histology and bone mineral densit... more Conclusions. This study demonstrates that alkaline therapy Bone histology and bone mineral density after correction of corrects abnormal bone cell function and elevates bone mineral acidosis in distal renal tubular acidosis. density in dRTA patients, indicating the causal role of acidosis Background. The association between chronic metabolic acin the alterations of bone cell functions and reduction in bone idosis and alterations in bone cell functions has been demonmineral density. Parathyroid gland activity also may be involved strated in vitro and in animal studies. However, the causal role in the adaptation of the body to chronic metabolic acidosis. of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density Distal renal tubular acidosis (dRTA) is a condition and bone histology before and after correction of acidosis among associated with impaired renal acid excretion, resulting patients with distal renal tubular acidosis (dRTA) in accumulation of acid in the body. The disease is associ-Methods. Correction of metabolic acidosis by potassium ciated with growth retardation [1], skeletal pain, abnormal trate was done in non-azotemic dRTA patients, 6 females and bone metabolism, and pathologic fractures [2, 3]. Our 4 males, who had never received long-term alkaline therapy previous study on bone mineral metabolism in patients before enrolling into this study. Blood chemistries, serum intact with dRTA demonstrated significant suppression in both parathyroid hormone, and 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, potassium, bone formation and bone resorption in association with bone mineral density determination, and transiliac bone biopsy mild elevation in osteoid volume [3]. Most dRTA patients were done in all patients at baseline and after one year of also had a marked reduction in bone mineral density of potassium citrate therapy. spine and hip [3]. A putative causal role of metabolic Results. Significant elevations in serum bicarbonate (16.5 Ϯ acidosis in the development of skeletal growth retardation 3.0 vs. 24.6 Ϯ 2.8 mEq/L, P Ͻ 0.05) and urinary potassium is supported by the fact that alkaline therapy normalized excretion (35.2 Ϯ 7.9 vs. 55.4 Ϯ3.5 mEq/L, P Ͻ 0.05) were observed after potassium citrate therapy. No significant alter
Journal of Bone and Mineral Research, Sep 1, 2003
This study demonstrated that there was extensive iron staining on trabecular surface and marked r... more This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF‐I was reduced and may modulate the reduction of bone mass.Introduction: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited. Therefore, this study was systematically conducted to determine the alterations in thalassemia patients.Methods: Serum biochemical parameters, trans‐iliac crest bone biopsy, and determination of bone mineral density of femur and lumbar spine were done in 18 thalassemic patients (10 females and 8 males).Results: Serum osteocalcin, carboxy terminal teleopeptide fragment of type I collagen, and parathyroid hormone levels were within normal limits, but serum 25(OH) vitamin D (19.3 ± 1.6 ng/ml) and 1,25(OH)2 vitamin D (33.77 ± 1.51 pg/ml) levels were decreased. Serum insulin‐like growth factor I (IGF‐I; 145.2 ± 20 ng/ml) was suppressed, whereas serum ferritin (1366.6 ± 253.9 ng/ml) was markedly elevated. Reduced bone mineral density was found in all studied areas. Trabecular bone volume was significantly decreased (16.65 ± 1.12%), whereas bone formation rate, eroded surface, and other bone histomorphometric parameters were within normal limits. The trabecular bone volume varied significantly with bone mineral density of total femur (r = 0.48, p = 0.04). There was an extensive stainable iron surface on the mineral front (9–60%). Significant correlation between serum IGF‐I, serum ferritin, stainable iron surface, and bone mineral density, lumbar spine, and total femur were found. Serum IGF‐I correlated with trabecular bone volume (r = 0.6, p = 0.03), inversely with both serum ferritin level (r = −0.6, p < 0.01), and inversely with stainable iron surface (r = −0.53, p = 0.02). Multiple regression analysis demonstrated that IGF‐I was the only independent variable that determined bone mineral density of lumbar spine and total femur.Conclusion: Low bone mineral density and reduced trabecular bone volume with extensive iron deposition are the predominant findings in thalassemic patients. There was no evidence of increased bone resorption or mineralization defect. A reduction in circulatory IGF‐I may modulate the reduction of bone mass.
Revista del climaterio, 2003
Kidney International, Mar 1, 2001
regarding bone densitometric measurement in distal RTA has been published. Previous in vitro stud... more regarding bone densitometric measurement in distal RTA has been published. Previous in vitro studies sug
acidosis lowers circulating adiponectin through inhibition of adiponectin gene transcription
日本人類遺伝学会大会プログラム・抄録集, 2016
BMC Complementary and Alternative Medicine, Sep 23, 2015
Background: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented d... more Background: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis. Methods: A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated. Results: A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7 %) and 9/28 (32.1 %) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027). Conclusions: Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study [Clinicaltrials.Gov Identifier Nct01800487].
BioMed Research International, Feb 6, 2023
The inhibition of poly(ADP-ribose) polymerases (PARPs) and ataxia telangiectasia and Rad3-related... more The inhibition of poly(ADP-ribose) polymerases (PARPs) and ataxia telangiectasia and Rad3-related (ATR) would be an alternative approach for cancer treatments. The aim of this study is to investigate the synergy of the different combinations of PARP inhibitors (olaparib, talazoparib, or veliparib) and ATR inhibitor AZD6738. A drug combinational synergy screen that combines olaparib, talazoparib, or veliparib with AZD6738 was performed to identify the synergistic interaction, and the combination index was calculated to verify synergy. TK6 isogenic cell lines with defects in different DNA repair genes were used as a model. Cell cycle analysis, micronucleus induction, and focus formation assays of serine-139 phosphorylation of the histone variant H2AX demonstrated that AZD6738 diminished G2/M checkpoint activation induced by PARP inhibitors and allowed DNA damage-containing cells to continue dividing, leading to greater increases in micronuclei as well as doublestrand DNA breaks in mitotic cells. We also found that AZD6738 was likely to potentiate cytotoxicity of PARP inhibitors in homologous recombination repair deficiency cell lines. AZD6738 sensitized more genotypes of DNA repair-deficient cell lines to talazoparib than to olaparib and veliparib, respectively. The combinational approach of PARP and ATR inhibition to enhance response to PARP inhibitors could expand the utility of PARP inhibitors to cancer patients without BRCA1/2 mutations.
Annals of Translational Medicine, Sep 1, 2017
BackgroundCytotoxic chemotherapy and/or radiation therapy inducing DNA damage is a part of cancer... more BackgroundCytotoxic chemotherapy and/or radiation therapy inducing DNA damage is a part of cancer treatment. Tripartite motif 29 (TRIM29) is highly expressed in many malignancies; for example, pancreatic cancer which is notorious resistant to cytotoxic chemotherapy and radiation therapy. TRIM29 is a member of the TRIM protein family composed of more than 70 members associated with a broad of biological processes. Originally, TRIM29 gene was described as a candidate gene responsible for ataxia- telangiectasia (AT); however, TRIM29 was dismissed as AT-causing gene after ataxia- telangiectasia mutated (ATM) was discovered as a causative gene for AT. A few studies about TRIM29 suggested that it was involved in DNA damage response and high expression of TRIM29 promoted resistance to ionizing radiation (IR), which induces DNA double strand breaks (DSB). Nevertheless, the functions of TRIM29 in DNA damage responses and/or DNA repair mechanisms are still unclear.MethodsTo investigate the functions of TRIM29 in DNA repair mechanisms, wild-type DT40 (WT) and mutant strains have been selected and used as a model. Firstly, the researchers generated the TRIM29 knockout (TRIM29-/-/-/+).ResultsThe growth analysis showed that TRIM29-/-/-/+ was comparable to WT. The results of DNA-damaging agent sensitivity using clonogenic survival assays indicated that TRIM29-/-/-/+ clones displayed increased sensitivity to topoisomerase 2 inhibitors which induce DNA DSBs repaired by non-homologous end joining (NHEJ) pathway. The TRIM29-/-/-/+ clones also exhibited mild sensitivity to camptothecin and cisplatin, indicating that TRIM29 plays a role in DNA DSB repair mechanisms.ConclusionsFurther study of TRIM29 in response to DNA DSBs may help improve the understanding of functions of TRIM29. In the future, TRIM29 might be a target for anti-cancer drug, leading to improvement of cancer treatment effectiveness.
PubMed, 2023
Cancer is the leading cause of death worldwide, resulting in the mortality of more than 10 millio... more Cancer is the leading cause of death worldwide, resulting in the mortality of more than 10 million people in 2020, according to Global Cancer Statistics 2020. A potential cancer therapy involves targeting the DNA repair process by inhibiting PARP-1. In this study, classification models were constructed using a non-redundant set of 2018 PARP-1 inhibitors. Briefly, compounds were described by 12 fingerprint types and built using the random forest algorithm concomitant with various sampling approaches. Results indicated that PubChem with an oversampling approach yielded the best performance, with a Matthews correlation coefficient > 0.7 while also affording interpretable molecular features. Moreover, feature importance, as determined from the Gini index, revealed that the aromatic/cyclic/heterocyclic moiety, nitrogen-containing fingerprints, and the ether/aldehyde/alcohol moiety were important for PARP-1 inhibition. Finally, our predictive model was deployed as a web application called PARP1pred and is publicly available at https://parp1pred.streamlitapp.com, allowing users to predict the biological activity of query compounds using their SMILES notation as the input. It is anticipated that the model described herein will aid in the discovery of effective PARP-1 inhibitors.
FEBS Open Bio, Aug 31, 2020
ɣ-H2AX phosphorylated H2A histone family member X 53BP1 tumor suppressor p53-binding protein 1 al... more ɣ-H2AX phosphorylated H2A histone family member X 53BP1 tumor suppressor p53-binding protein 1 alt-EJ alternative end joining ATDC ataxia telangiectasia group D complementing protein ATM ataxia telangiectasia mutated BASC BRCA1-associated surveillance complex