ingrid falnoga - Academia.edu (original) (raw)

Papers by ingrid falnoga

PubMed, 2001

The action of mercuric chloride and methyl mercuric chloride on the membrane lateral domain organ... more The action of mercuric chloride and methyl mercuric chloride on the membrane lateral domain organization of bovine, equine, and canine erythrocytes was studied. Electron paramagnetic resonance (EPR) spectra of spin-labeled erythrocytes were analyzed with respect to their lateral domain structure. Continuous alteration of the membrane domain populations revealed that mercuric compounds affect the membrane via the evolution of toxic events in the cells.

Journal de physique, May 1, 2003

Mercury contamination of local foodstuffs bas been investigated in an area highly polluted with m... more Mercury contamination of local foodstuffs bas been investigated in an area highly polluted with mercury due to the former Idrija mercury mine activities from 1508-1994. The contents of mercury were checked in selected samples of seasonal vegetables. Determinations of selenium were included due to its beneficial effects against mercury toxicity in living organisms. The most interesting observation was that in carrot an increase of Hg content was accompanied by decrease of Se.

Lipids, 2005

Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three com... more Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three common alleles (ε2, ε3, and ε4). Population studies have shown that the risk of diseases characterized by oxidative damage, such as coronary heart disease and Alzheimer's disease, is significantly higher in ɛ4 carriers. We evaluated the association between apoE genotypes and plasma F2‐isoprostane levels, an index of lipid peroxidation, in humans. Two hundred seventy‐four healthy subjects (104 males, 170 females; 46.9±13.0 yr; 200 whites, 74 blacks; 81 nonsmokers, 64 passive smokers, and 129 active smokers) recruited for a randomized clinical antioxidant intervention trial were included in this analysis. ApoE genotype was determined by PCR and restriction enzyme digestion. Free plasma F2‐isoprostane was measured by GC‐MS. Genotype groups were compared using multiple regression analysis with adjustment for sex, age, race, smoking status, body mass index, plasma ascorbic acid, and β‐carote...

Biological Trace Element Research, 2000

Using various chromatographic techniques (size exclusion, anion exchange, and cation exchange) co... more Using various chromatographic techniques (size exclusion, anion exchange, and cation exchange) combined with several detectors (neutron activation analysis and atomic fluorescence spectrometry), an attempt was made to characterize selenium compounds in some edible, selenium-accumulating mushrooms (Albatrellus pes-caprae and Boletus edulis). The mushrooms contained mostly low-molecular-weight (6 kDa) selenium compounds. After proteolysis, only a small fraction of the extractable selenium could be identified as selenite (3.0-9.2%, Albatrellus pes-caprae), selenocystine (minor, Albatrellus pes-caprae; 7.5%, Boletus edulis), or selenomethionine (1.0%, Boletus edulis), leaving the form of the bulk still to be elucidated.

Environmental Research, Mar 1, 2023

Blood, Dec 6, 2014

Introduction Arsenic trioxide (ATO) has been shown to be effective in the treatment of acute prom... more Introduction Arsenic trioxide (ATO) has been shown to be effective in the treatment of acute promyelocytic leukemia (APL) and towards multiple myeloma (MM) cells. Biologically active form of ATO is inorganic arsenic in its trivalent form (AsIII) which is metabolised in more or less active metabolites already in hours after infusion. The major arsenic excretion metabolites are methylated, namelly methylarsonic acid (MA) and dimethylarsinic acid (DMA). Despite that ATO already has an established role in APL treatment, there is still a lack of data on its metabolism especially when it is combined with other active compounds. The aim of our study was to get an insight into ATO metabolism through measurement of its metabolites in urine and total arsenic in blood during treatment according two different protocols. Patients and methods Patients (8 APL, 12 MM) were treated by ATO (administered as 2 h intravenous infusion) during the years 2004 - 2014. APL patients were previously treated according to a standard APL EORTC protocol. In three patients ATO was started immediately after an interruption of treatment due to a differentiation syndrome and in the remaining five patients ATO was started due to relapse. ATO (0.15 mg/L) was administered for i) 50 consecutive days and prolonged for 25 days (5 days/week) after 3 weeks break or for ii) 25 consecutive days repeated after one week break. Majority of 12 MM patients was heavily pretreated, relapsed or refractory. ATO (0.25 mg/kg) infusion was followed by injection of ascorbic acid (1g). Melphalan (0.1 mg/kg) or Dexamethasone (40 mg/kg) was added in MAC or DAC scheme respectively. ATO was given in cycles (4 consecutive days followed by 3 weeks of 2 applications/week). Treatment efficacy was evaluated by measurement of a monoclonal spike except for patients with Bence-Jones type of MM who were only clinically evaluated. The urine samples were taken before ATO infusion and analysed using HPLC separation combined on-line with hydride generation and atomic fluorescence spectrometry. Arsenic species As(III) and As(V) and both methylated metabolites MA and DMA were followed. Total arsenic concentrations in serum were analysed by ICP-MS. Results All APL patients have obtained a stable molecular remission. In contrast, efficacy of ATO treatment in MM patients is difficult to be evaluated due to the patients’ initial poor condition. In three MM patients effect of ATO cannot be evaluated since they deceased during the treatment. In four out of 9 remaining MM patients at least a partial remission was obtained. Differences between both groups, or better between both protocol regimens (consecutive APL or pulse DAC/MAC in MM), are also reflected in As serum levels and in the presence of ATO metabolites in urine. During the therapy the residual As serum levels in APL group were almost two times as big as those in MM group (72,33±16.79 ng/g vs. 45.13±7.2 ng/g). That means that lower daily doses of ATO preserve higher As concentrations in time than pulse therapy with higher doses. In the urine of MAC/DAC group the proportion of DMA was higher than in the patients treated according APL protocol (48.7 ± 14.6 % vs 63.2 ± 10.4%, Figure 1), while proportions of other three metabolites were lower. A higher proportion of the main active component, As(III), was present in the body of APL patients in comparison to MAC/DAC treated MM patiens (17.5 ± 7.4 % vs 8.6 ± 4.5 %; Figure 1). Differences in metabolites between both groups were statistically significant (MA: P = 0.0127; AsIII, DMA, AsIII: P…

Pure and Applied Chemistry, Jan 6, 2012

The objectives of this work were to get information on Zn species in two different specimens of e... more The objectives of this work were to get information on Zn species in two different specimens of edible plants (pumpkin seeds and iceberg lettuce) and simulation of their behavior in the human gastrointestinal tract. An array of analytical techniques was used to aid in this research: ultrasound-assisted variable volume extraction, size exclusion chromatography (SEC), and physiologically based extraction tests (PBETs); elemental detection was performed by inductively coupled plasma-mass spectrometry (ICP-MS). Results show that pumpkin seeds and iceberg lettuce have different Zn species fingerprints (in water extracts) with a high (ca. 70 %) low-molecular-weight fraction (ca. 500 Da) in iceberg lettuce and a high (ca. 60 %) intermediate/high-molecular-weight fraction (10-20 kDa) in pumpkin seeds. When these Zn species are subjected to conditions simulating the human stomach (pH ~ 2) complete scrambling to their basic ionic form (Zn 2+) takes place. Under conditions simulating the digestion in the intestines (pH ~ 7) formation of insoluble Zn complexes occurs, especially for pumpkin seeds, which may be related to antinutrients like naturally present phytate, leading to reduced Zn bioaccessibility in the small intestine.

Environment International, 2022

Single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYPs) and UDP-glucuronosyltransferase ... more Single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYPs) and UDP-glucuronosyltransferase (UGTs) genes have been proposed to influence phthalates and 1,2-cyclo-hexanedicarboxylic acid diisononyl ester (DINCH) biotransformation but have not been investigated on a populational level. We investigated the role of SNPs in CYP2C9, CYP2C19, CYP2D6, UGT2B15, and UGT1A7 genes in the biotransformation of phthalates (DEHP, DEP, DiBP, DnBP, BBzP, DiNP, DidP) and DINCH by determining their urine metabolites. From the Slovenian study population of 274 men and 289 lactating primiparous women we obtained data on phthalate and DINCH urine metabolite levels (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, MEP, MiBP, MnBP, MBzP, cx-MINP, OH-MiDP, MCHP, MnPeP, MnOP, 5OH-MINCH, 5oxo-MINCH), SNP genotypes (rs1057910 = CYP2C9*3, rs1799853 = CYP2C9*2, rs4244285 = CYP2C19*2, rs12248560 = CYP2C19*17, rs3892097 = CYP2D6*4, rs1902023 = UGT2B15*2, and rs11692021 = UGT1A7*3) and questionnaires. Associations of SNPs with levels of metabolites and their ratios were assessed by multiple linear regression and ordinary logistic regression analyses. Significant associations were observed for CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs. The most pronounced was the influence of CYP2C9*2 and *3 on the reduced DEHP biotransformation, with lower levels of metabolites and their ratios in men and women. In contrast, carriers of CYP2C19*17 showed higher urine levels of DEHP metabolites in both genders, and in women also in higher DiNP, DiDP, and DINCH metabolite levels. The presence of UGT1A7*3 was associated with increased metabolite levels of DINCH in men and of DiBP and DBzP in women. Statistical models explained up to 27% of variability in metabolite levels or their ratios. Our observations confirm the effect of CYP2C9*2 and *3 SNPs towards reduced DEHP biotransformation. We show that CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs might represent biomarkers of susceptibility or resilience in phthalates and DINCH exposure that have been so far unrecognised.

Environmental Research, 2017

Background: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot sampl... more Background: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples. Aim: To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females, mean age 29 years; 2007-2015) who have not been exposed to Cd occupationally. Results: Geometric means (GMs) of Cd in blood and spot urine samples were 0.27 ng/mL (0.28 for males and 0.33 for females) and 0.19 ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (β=0.11, p=0.002 for males and β=0.33, p < 0.001 for females) and for females between urine NAG and blood Cd (β=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p < 0.05, β=0.11-0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced by current smoking and blood Pb in males and by pre-pregnancy smoking and blood Se in females (β up to 0.34, p < 0.001). Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses data with unnormalised were taken as more valid. Conclusions: The observed uncertainties introduced by urine normalisation, particularly by creatinine, confirm blood Cd as a superior low-Cd exposure biomarker versus urine Cd in cases when 24 h urine is unattainable. Evidence that A1M can be positively related to Cd, smoking (current or pre-pregnancy), Pb, and Se status, points to the versatile biological functions of A1M.

Biological Trace Element Research, 2002

In plasma, Se is found in plasma glutathione peroxidase (pGSH-Px), selenoprotein P (Sel-P), and a... more In plasma, Se is found in plasma glutathione peroxidase (pGSH-Px), selenoprotein P (Sel-P), and albumins. The aim of the present study was to determine the influence of lifelong exposure to various levels of mercury vapor (Hg 0) on plasma Se content and the fraction bound to Sel-P. Second, a pilot study was performed on the influence of short-term excessive physical stress and metal chelation (DIMAVAL) treatment. Samples of human plasma/serum obtained from a control group, Idrija residents living in a Hg-polluted environment because of the vicinity of the Idrija mercury mine (closed 1994), a few Idrija residents exposed to excessive physical stress, and two retired miners treated with the drug DIMAVAL were investigated. Selenoprotein P was isolated by affinity chromatography (heparin-Sepharose), and the concentrations of selenium were determined by radiochemical neutron activation analysis and hydride generation-atomic fluorescence spectrometry. Regardless of the group investigated, plasma Se average values were very similar (about 70-90 ngSe/g). A significant change of Sel P (7-24% decrease) was noted only in the group exposed to physical stress as compared to the same subjects before the test, to the control group, and to the Hg exposed group. The decrease of Se bound on Sel-P was accompanied by its increase in fraction of pGSH-Px with albumin.

Food Chemistry, Oct 1, 2011

Pumpkin seeds are one of the foodstuffs recommended in diets which do not contain other Zn-rich s... more Pumpkin seeds are one of the foodstuffs recommended in diets which do not contain other Zn-rich sources. The main objectives of this work were to get information on Zn and its species in pumpkin seeds, and their possible degradation in the human gastrointestinal tract, indicative of Zn bioaccessibility. A sequential analytical approach was applied, focusing on total Zn, spatial Zn distribution, extractability, speciation and bioaccessibility of Zn and its species. It was shown that water extracts of pumpkin seeds exhibit a specific Zn species fingerprint with ca. 30% of a low-MW fraction (0.5-2 kDa) and ca. 60% of an intermediate/high-MW fraction (10-20 kDa). Digestion of Zn species under simulated stomach conditions proved that Zn species identified in plant extracts were completely decomposed to Zn 2+. The subsequent digestion under intestinal conditions showed that Zn becomes less accessible, indicating that antinutrients like naturally present phytate may be responsible for complex formation in the small intestines, thus reducing the potential for Zn bioavailability.

Fresenius Journal of Analytical Chemistry, Mar 2, 2000

The purpose of the study was to optimise analytical methods for determination of the chemical spe... more The purpose of the study was to optimise analytical methods for determination of the chemical speciation of mercury in studies of protective mechanisms of selenium. Optimisation of the methods was performed using CRM DOLT-2 (Dogfish liver), both in its original form and after separation of various fractions. The sample was homogenised with 10 mM Tris-HCl buffer (pH 7.6) and ultracentrifuged. The soluble phase obtained was applied to a size exclusion chromatography column (Sephadex G-75 column) for separation of various protein fractions. Total mercury (total Hg), monomethyl mercury (MeHg) and selenium (Se) were determined in whole dogfish liver tissue and its soluble and insoluble phases (pellet). Different approaches for determination of total Hg and MeHg were compared. Simultaneous determination of MeHg and inorganic mercury (Hg 2+) was based on alkaline dissolution and/or acid leaching, followed by ethylation, room temperature precollection, isothermal gas chromatography (GC), pyrolysis and detection with cold vapour atomic fluorescence spectrometry (CVAFS). The sum of MeHg and Hg 2+ was compared to total Hg results obtained by acid digestion and CVAAS detection. The accuracy of MeHg determination was checked by its determination using acid leaching at room temperature, solvent extraction, back extraction into Milli-Q water, ethylation, GC and CVAFS detection. For the insoluble phase it is recommended to use solvent extraction for MeHg and acid digestion CVAAS for total Hg. For determination of MeHg and Hg 2+ in the lyophilised sample and water soluble fractions containing low concentrations of mercury species, the simultaneous measurement of MeHg and Hg 2+ after alkaline dissolution is the most appropriate method.

Biometals, Aug 28, 2011

This work presents an analytical chemist's view on the sometimes unconscious use of arsenic triox... more This work presents an analytical chemist's view on the sometimes unconscious use of arsenic trioxide in (bio)medical research. Arsenic trioxide is a frequently used chemical in cancer treatment research and its action to various malignant cells has been extensively studied and published. Unfortunately some research articles show trivial errors with regards to background knowledge of the chemical, handling the chemical, experimental design and interpretation of results like e.g. in a range of articles comparing advantages of tetraarsenic oxide over arsenic trioxide (dimeric/monomeric) although the dissolution of both yields the same active compound (HAsO 2). To fully understand the implications of these errors we will highlight some of them with the intent to harmonize future work in this field.

Food Chemistry, Apr 1, 2021

A survey of highly toxic arsenic compounds, together with some other elements was carried out on ... more A survey of highly toxic arsenic compounds, together with some other elements was carried out on 40 polished rice samples (white, basmati and parboiled) and 10 brown rice samples from the Slovenian market. The average total As concentration was 157 ± 60 μg kg −1 ; highest levels were found in parboiled and brown rice and lowest in basmati. The average inorganic As concentration was 90 ± 35 μg kg −1. Dimethylarsinic acid and monomethylarsonic acid, which also exhibit high toxicity levels in some cases constitute > 50% of total arsenic and might deserve more attention. Contrary to other foods, the total arsenic concentration in rice may even be a better health hazard indicator than the inorganic arsenic concentration. Elemental analysis of rice revealed large differences between polished and brown rice, especially for Mg, Mn, P, Fe and K, which were 2-4 times higher in brown rice than in polished rice.

Biological Trace Element Research, Sep 29, 2011

Various biomarkers were used to assess selenium (Se) status during 3 months of basic military tra... more Various biomarkers were used to assess selenium (Se) status during 3 months of basic military training in a group of recruits. Samples of whole blood and plasma or serum were taken from a group of conscripts three times: at the beginning (n = 15), in the middle immediately after a severely stressful physical activity (n = 15) and at the end of military training (n = 13). Selenium was determined in diet samples, blood, plasma and plasma protein fractions as selenoprotein P (SelP) and glutathione peroxidase (eGPx). Selenium was determined by hydride generation-atomic fluorescence spectrometry and fractionation of proteins performed by affinity chromatography. Total serum glutathione, erythrocyte and serum GPx activity were followed as well. The average Se intake was calculated according to meal consumption questionnaires and Se determined in composite diet samples, giving an assessed intake of 48 ± 10 μg/day. At all three samplings, the average blood Se concentration was within the framework of adequate supply (87 ± 12, 94 ± 15 and 80 ± 13 ng/g). Plasma Se was between 70 and 80 ng/g (71 ± 10, 79 ± 9 and 76 ± 10 ng/g), which is believed to enable the full expression of plasma GPx. The average shares of plasma Se proteins were 61 ± 6%, 58 ± 6% and 54 ± 9% for SelP and 27 ± 4%, 34 ± 7% and 29 ± 5% for GPx. Although the observed tendency of the increases of serum and erythrocyte GPx activities at the second and third samplings with respect to the first was statistically insignificant, it is still indicative of some protection against oxidative stress, while the decreasing SelP levels during training suggest a slowly decreasing biologically active selenium pool.

Environmental Research, May 1, 2009

The main objectives of our study were to estimate the impact of a mercury cell chlor-alkali (MCCA... more The main objectives of our study were to estimate the impact of a mercury cell chlor-alkali (MCCA) complex in Rosignano Solvay (Tuscany, Italy) on the local environment and to assess mercury exposure of inhabitants living near the plant. Measurement campaigns of atmospheric Hg near the MCCA plant showed that the impact of the emitted Hg from the industry on the terrestrial environment is restricted to a close surrounding area. Total gaseous mercury concentrations in ambient air of inhabited area around the MCCA plant were in the range of 8.0-8.7 ng/m 3 in summer and 2.8-4.2 ng/m 3 in winter. Peaks of up to 100 ng/m 3 were observed at particular meteorological conditions. Background levels of 2 ng/m 3 were reached within a radius of 3 km from the plant. Reactive gaseous mercury emissions from the plant constituted around 4.2% of total gaseous mercury and total particulate mercury emission constituted around 1.0% of total gaseous mercury emitted. Analysis of local vegetables and soil samples showed relatively low concentrations of total mercury (30.1-2919 mg Hg/kg DW in the soil; o0.05-111 mg Hg/kg DW in vegetables) and methylmercury (0.02-3.88 mg Hg/kg DW in the soil; 0.03-1.18 mg Hg/kg DW in vegetables). Locally caught marine fish and fresh marine fish from the local market had concentrations of total Hg from 0.049 to 2.48 mg Hg/g FW, of which 37-100% were in the form of methylmercury. 19% of analysed fish exceeded 1.0 mg Hg/g FW level, which is a limit set by the European Union law on Hg concentrations in edible marine species for tuna, swordfish and shark, while 39% of analysed fish exceeded the limit of 0.5 mg Hg/g FW set for all other edible marine species. Risk assessment performed by calculating ratio of probable daily intake (PDI) and provisional tolerable daily intake (PTDI) for mercury species for various exposure pathways showed no risks to human health for elemental and inorganic mercury, except for some individuals with higher number of amalgam fillings, while PDI/PTDI ratio for methylmercury and total mercury exceeded the toxicologically tolerable value due to the potential consumption of contaminated marine fish.

$Research paper thumbnail of A study of low level selenium determination by hydride generation atomic fluorescence spectrometry in water soluble protein and peptide fractions$

Analytical and Bioanalytical Chemistry, Dec 1, 2003

Development of a method for very low level selenium determination in water soluble protein and pe... more Development of a method for very low level selenium determination in water soluble protein and peptide fractions, obtained after various separation procedures, is presented. A hydride generation atomic fluorescence spectrometry (HG-AFS) detection system was optimised and the influence of Cu(II), Sb(V), As(III) and HNO3 interferences in the measurement of Se by HG-AFS was investigated. A destruction procedure using HNO3 and H2O2 was also optimised and the average recovery of the digestion of a solution of selenomethioneine was 92 +/- 4% (n=14). Combination of this digestion with the detection system gave reliable results. Accuracy was tested by comparison with two independent methods. A very low detection limit (DL) of 0.2 ng/g of measuring solution was achieved. The whole procedure from weighing to measuring was performed in the same Teflon tube. The addition of HNO3 to the fractions before long term storage at -20 degrees C was necessary to prevent adsorption on the test tubes. Selenium was measured in water soluble protein and peptide fractions obtained after extraction, and Sephadex G-75 chromatography performed on liver samples from: i) hens exposed to As2O3, ii) hens fed with a high fat feed and iii) the certified reference material dogfish liver (CRM DOLT-2). Because of the very low DL we were able to observe the Se distribution in chromatographic fractions of samples of organisms which were not exposed to excess amounts of Se. The presence of selenium associated with metallothioneins was observed.

Issues in toxicology, 2011

Arsenic is a potentially toxic element to humans, animals and plants. Exposure of humans to arsen... more Arsenic is a potentially toxic element to humans, animals and plants. Exposure of humans to arsenic and its compounds may originate from both natural and anthropogenic sources, including industrial activities, and consumption of food and beverages. Arsenic is found in nature in a variety of inorganic and organic compounds. The distribution, mobility, and toxicity of arsenic in nature are species dependent. For example, inorganic arsenic species are generally much more toxic than organic species, and of these trivalent arsenic species (arsenite and methylated arsenic compounds) are much more toxic than pentavalent (arsenate and methylated compounds), while arsenobetaine and arsenocholine are considered to be non-toxic. Inorganic arsenic is also known to be carcinogenic in humans. Therefore, speciation of arsenic is essential in providing an accurate assessment of environmental and human health risks, rather than using only total arsenic concentrations as has been the practice for many years. There are three population groups at high exposure risk: (1) the occupationally exposed, (2) people drinking water with abnormally high concentrations of arsenic, (3) children living in the close vicinity of arsenic contaminated (copper) smelters. Hair, nail, blood and mainly urine can be analysed to monitor exposure to inorganic arsenic. However, matrix complexity often prevents complete identification of arsenic compounds (speciation) so that only total arsenic can be determined in non-liquid biological samples. Arsenic species are more easily determined in blood and urine; nevertheless, for kinetic reasons, the determination of urinary metabolites is preferred for the biomonitoring of exposure to arsenic.

Biometals, Dec 15, 2015

Arsenic trioxide (As(III) in solution) has been shown to be the most active single agent in comba... more Arsenic trioxide (As(III) in solution) has been shown to be the most active single agent in combating acute promyelocytic leukemia (APL). It is metabolized and excreted via urine as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and As(V), along with excess As(III). In our study eight APL patients were treated (intravenously) with 0.15 mg As2O3/kg/day. During the therapy As(III) and its metabolites were followed in pre- and post-infusion urine using HPLC for separation followed by on-line detection using hydride generation-atomic fluorescence spectrometry. Five patients had a normal excretion pattern of residual arsenic compounds in morning pre-infusion urine, with 15-25 % of As(III), 35-55 % of DMA, 25-30 % of MMA and 1-5 % of As(V), while three patients showed unexpected exceptions from typical excretion patterns of arsenic compounds (i) a high DMA/MMA ratio (factor 5.3), (ii) severe As(III) oxidation (10.2 % As(III) converted to As(V)) or (iii) the presence of an excessive amount of As(III) (average 30.4 % of total arsenic). Intriguing was the occurrence of post-infusion oxidation of As(III) to As(V) observed in almost all patients and being especially high (&amp;amp;amp;amp;amp;amp;amp;gt;40 %) in patient with increased residual As(V). Results indicate that arsenic metabolites patterns can be unpredictable. Observed high levels of un-metabolised As(III) are a warning signal for side effects and for routine determination of arsenic metabolites during first days of treatment. High or low percentages of MMA or DMA did not show any observable effect on treatment results, while clear presence of post-infusion As(V) supports theoretical claims of in vivo oxidation (detoxification) of As(III) to As(V) associated with various metabolic processes.