Effect of N-acetyl-L-cysteine on human chronic myeloid leukemia cells KCL22 treated with mitomycin C (original) (raw)
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Arhiv za higijenu rada i toksikologiju, 2004
Although chemotherapy targets cancer tissue, it also damages the DNA of non-cancer cells. The aim of this study was to evaluate the in vitro genotoxic potential of therapeutic concentrations of bleomycin and mitomycin C, added alone or in combination to cultures of human peripheral lymphocytes. The levels of DNA damage and repair were assessed using the alkaline comet assay immediately after cell treatment as well as 24 and 48 hours following treatment. The results indicate that individual drugs and their combination induce a significant DNA damage to peripheral blood lymphocytes. Bleomycin alone induced the highest levels of primary DNA damage immediately after cell treatment. Although mitomycin C alone induced massive cross-linking and retarded DNA migration in resting cells, active proliferation and repair processes significantly increased DNA damage. Combined, they showed a synergetic effect, inducing complex patterns of DNA damage in peripheral blood lymphocytes and producing d...
Experimental and Toxicologic Pathology, 2010
Mitomycin C (MMC) is an antineoplastic agent used to fight a number of different cancers including cancer of the stomach, colon, rectum, pancreas, breast, lung, uterus, cervix, bladder, head, neck, eye and oesophagus. It is a potent DNA cross-linker. The prolonged use of the drug may result in permanent bone marrow damage and other various types of secondary tumors in normal cells. The toxic effect of anticancerous drugs may be reduced if supplemented with natural antioxidants/plant products. With this view, the effect of 5, 10 and 15 mM of curcumin was studied against the genotoxic doses of MMC, i.e. 10 and 20 mM, in cultured human lymphocytes using cell viability, lipid peroxidation and DNA damage quantification as parameters. The treatment of curcumin with MMC results in a significant dosedependent increase in cell viability and decrease in lipid peroxidation and DNA damage suggesting a protective role of curcumin against the anticancerous drug mitomycin C.
Mitomycin C-induced damage and repair in human and pig lymphocytes
Mutation research, 1986
Human and pig lymphocytes were used to compare the chromosomal sensitivity to MMC and the efficiency of repair of MMC-induced DNA adducts. No significant interspecies differences were found. The results obtained show that SCE frequencies are linearly correlated with MMC doses. During the G0 period there are indications that lymphocytes may half-repair the DNA-interstrand crosslinks transforming bi- into mono-adducts. SCEs induced by MMC decrease to near control levels in the second cell cycle. Therefore, most MMC lesions responsible for SCEs should be repaired between the moment in the first S phase in which they induce the exchanges and the onset of the second S period.
Modulation of Mitomycin C-induced Genotoxicity by Acetyl- and Thio- Analogues of Salicylic Acid
Background: Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the antigenotoxic potential of ASA and TSA. Materials and Methods:
Determination of DNA Damage in Experimental Liver Intoxication and Role of N-Acetyl Cysteine
Cell Biochemistry and Biophysics, 2014
The present study aimed at detecting DNA damage and fragmentation as well as histone acetylation depending on oxidative stress caused by CCl 4 intoxication. Also, the protective role of N-acetyl cysteine, a precursor for GSH, in DNA damage is investigated. Sixty rats were used in this study. In order to induce liver toxicity, CCl 4 in was dissolved in olive oil (1/1) and injected intraperitoneally as a single dose (2 ml/kg). N-acetyl cysteine application (intraperitoneal, 50 mg/kg/day) was started 3 days prior to CCl 4 injection and continued during the experimental period. Control groups were given olive oil and Nacetyl cysteine. After 6 and 72 h of CCl 4 injection, blood and liver tissue were taken under ether anesthesia. Nuclear extracts were prepared from liver. Changes in serum AST and ALT activities as well as MDA, TAS, and TOS levels showed that CCl 4 caused lipid peroxidation and liver damage. However, lipid peroxidation and liver damage were reduced in the N-acetyl cysteine group. Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl 4 intoxication induces oxidative stress and apoptosis in rat liver. The results of the present study indicate that N-acetyl cysteine has a protective effect on CCl 4 -induced DNA damage.
Mitomycin induced apoptosis in human leukemia K562 cells
Objective: The research aimed to study the effects of mitomycin on human leukemic K562 cells, and to explore the mechanism of mitomycin induced apoptosis．In order to provide previous experiment basis for mitomycin applying clinical treatments Methods: The multiplication and apoptosis status of K562 cells treated different time by different concentration mitomycin were observed by light microscope, fluorescence microscope, TEM, agrose gel electrophoresis of DNA and flow cytometry. Results: The results showed that mitomycin could induce K562 cells apoptosis, and the best concentration was 12.5µg/ml for 48 h. The optimal concentration of apoptosis induced by apoptosis rate is (28.8±1.04) % (P<0.01) . Mitomycin could affect the S phase among cellular multiplication, cell could be blocked by mitomycin and then apoptosis in this phase. Conclusions: Mitomycin can induce the apoptosis of human leukemic K562 cells. It is of great significance to guide clinical medication.
Journal of Biological Chemistry, 2004
The effects of the subcellular localization of overexpressed bioreductive enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) on the activity of the antineoplastic agent mitomycin C (MC) under aerobic and hypoxic conditions were examined. Chinese hamster ovary (CHO-K1/dhfr(-)) cells were transfected with NQO1 cDNA to produce cells that overexpressed NQO1 activity in the nucleus (148-fold) or the cytosol (163-fold) over the constitutive level of the enzyme in parental cells. Subcellular localization of the enzyme was confirmed using antibody-assisted immunofluorescence. Nuclear localization of transfected NQO1 activity increased the cytotoxicity of MC over that produced by overexpression in the cytosol under both aerobic and hypoxic conditions, with greater cytotoxicity being produced under hypoxia. The greater cytotoxicity of nuclear localized NQO1 was not attributable to greater metabolic activation of MC but instead was the result of activation of the drug in close proximity to its target, nuclear DNA. A positive relationship existed between the degree of MC-induced cytotoxicity and the number of MC-DNA adducts produced. The findings indicate that activation of MC proximal to nuclear DNA by the nuclear localization of transfected NQO1 increases the cytotoxic effects of MC regardless of the degree of oxygenation and support the concept that the mechanism of action of MC involves alkylation of DNA.