Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.     

Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean population

The relationship of inorganic arsenic exposure through drinking water and total urinary arsenic excretion in a nonoccupationally exposed population was evaluated in a cross-sectional study in three mayor cities of Chile (Antofagasta, Santiago, and Temuco). A total of 756 individuals in three population strata (elderly, students, and workers) provided first morning void urine specimens the day after exposure and food surveys were administered. Arsenic intake from drinking water was estimated from analysis of tap water samples, plus 24-h dietary recall and food frequency questionnaires. Multilevel analysis was used to evaluate the effects of the age group and city factors adjusted by predictor variables. Arsenic levels in drinking water and urine were significantly higher in Antofagasta compared with the other cities. City-and individual-level factors, 12% and 88%, respectively, accounted for the variability in urinary arsenic concentration. The main predictors of urinary arsenic concentration were total arsenic consumption through water and age. These findings indicate that arsenic concentration in drinking water continues to be the principal contributing factor to exposure to inorganic arsenic in the Chilean population.     

Metabolism of inorganic arsenic in children with chronic high arsenic exposure in northern Argentina.

This study concerns the metabolism of inorganic arsenic (As) in children in three villages in northern Argentina: San Antonio de los Cobres and Taco Pozo, each with about 200 microg As/l in the drinking water, and Rosario de Lerma, with 0.65 microg As/l. Findings show that the concentrations of As in the blood and urine of the children in the two As-rich villages were on average 9 and 380 microg/l, respectively, the highest ever recorded for children. The concentrations were about 10 and 30 times higher for blood and urine, respectively, than in Rosario de Lerma. Total As in urine was only slightly higher than the sum of metabolites of inorganic As (U-Asmet), i.e., inorganic As, methylarsonic acid (MMA), and dimethylarsinic acid (DMA); this shows that inorganic As was the main form of As ingested. In contrast to previous studies on urinary metabolites of inorganic As in various population groups, the children and women in the present study excreted very little MMA. Thus, there seems to be a polymorphism for the enzymes (methyltransferases) involved in the methylation of As. Interestingly, the children had a significantly higher percentage of inorganic As in urine than the women, about 50% versus 32%. Also, the percentage of inorganic As in the children is considerably higher than in previous studies on children (about 13% in the two studies available) and adults (about 15-25%) in other population groups. This may indicate that children are more sensitive to As-induced toxicity than adults, as the methylated metabolites bind less to tissue constituents than inorganic As. In the children, the percentage inorganic arsenic in urine decreased, and the percentage of DMA increased with increasing U-Asmet, indicating an induction of As methylation with increasing exposure.     

Geographical and temporal differences in the urinary excretion of inorganic arsenic: a Belgian population study.

OBJECTIVE: This Belgian study assessed the geographical and temporal differences in the exposure of the population to inorganic arsenic, a known carcinogen. METHODS: In the CadmiBel study (1985-9) the 24 h urinary arsenic excretion was measured, as an index of recent exposure, in industrialised cities (Liège: n = 664, Charleroi: n = 291), in a rural control area (Hechtel-Eksel: n = 397), and in rural districts in which the population had possibly been exposed through the drinking water or the emissions of nonferrous smelters (Wezel: n = 93, Lommel: n = 111, and Pelt: n = 133). In the PheeCad study, in 1991-5, the rural areas (n = 609) were re-examined together with an urban control area (Leuven: n = 152). RESULTS: The CadmiBel results showed that after adjustment for sex, age, and body mass index, the 24 h arsenic excretion was on average low in Liège (91 nmol), Charleroi (155 nmol), Hechtel-Eksel (144 nmol), and Wezel (158 nmol), whereas the highest excretions were found in Lommel (570 nmol) and Pelt (373 nmol). During the PheeCad study, the mean 24 h arsenic excretion in the rural areas ranged from 81 to 111 nmol. This was lower than six years earlier and similar to the excretion in the control town (108 nmol). Longitudinal studies in 529 people living in the rural areas confirmed that their 24 h arsenic excretion had decreased (P < 0.001) from 222 to 100 nmol. As well as the drinking water, industry was likely to be a source of the increased exposure in Lommel and Pelt in 1985-9, because at that time the urinary arsenic excretion did not follow the regional differences in the arsenic content of the drinking water, because the fall in the arsenic excretion over time coincided with the implementation by industry of stricter environmental regulations, because in individual subjects the urinary arsenic excretion was inversely correlated with the distance to the nearest smelter, and because an increased arsenic excretion was only found downwind from the main smelter. The official network that monitors the arsenic concentration in airborne and fall out dust did not detect the high exposure in Lommel and Pelt between 1985 and 1989. CONCLUSION: This study highlights the necessity to validate environmental monitoring programmes by directly estimating the internal exposure of the population.     

Metabolism of 74As-labeled trivalent and pentavalent inorganic arsenic in mice

Man is exposed to different forms of arsenic in the environment but differences in metabolism and toxicity are poorly understood. The differences in metabolism between pentavalent and trivalent inorganic arsenic in mice following single oral administration of ⁷⁴As-labeled arsenate or arsenite (0.4 and 4 mg As/kg body wt) was studied. Valence state of the administered arsenic was strictly controlled, which has not always been the case in previous studies. In mice given the high dose, whole body retention was two to three times higher after exposure to As(III) compared to As(V). Retention was also dose dependent. Five weeks after administration, high dose/low dose retention ratios were 6 and 11 for As(V) and As(III). Differences found in most organs studied (blood, kidney, liver, bile, brain, skeleton, and skin) were most obvious in liver and bile with concentrations 2 to 10 times higher in the As(III) groups. Red cell/plasma ratios were 2–3 for As(III) and close to unity for As(V). It is suggested that the observed differences between As(V) and As(III) are due to differences in degree of methylation and subsequent elimination primarily via the kidneys.     

Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in Bangladesh

Although genetic polymorphisms have been shown to explain some of the large variation observed in the metabolism of inorganic arsenic there may be several other factors playing an important role, e.g. nutrition. The objective of this study was to elucidate the influence of various factors on current arsenic exposure and metabolism in Matlab, a rural area in Bangladesh, where elevated water arsenic concentrations and malnutrition are prevalent. In total 1571 individuals, randomly selected from all inhabitants above 5 years of age, were investigated by measuring arsenic in urine and drinking water. In a subset of 526 randomly selected individuals, arsenic metabolites were speciated using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). A significant association was observed between arsenic in urine and drinking water (R2=0.41). The contribution to urinary arsenic from arsenic exposure from food and other water sources was calculated to be almost 50microg/L. The individuals in the present study had remarkably efficient methylation, in spite of high exposure and prevalence of malnutrition. Gender and age were major factors influencing arsenic metabolism in this population with a median of 77microg/L of arsenic in urine (range: 0.5-1994microg/L). Women had higher arsenic methylation efficiency than men, but only in childbearing age, supporting an influence of sex hormones. Overall, exposure level of arsenic, gender and age explained at most 30% of the variation in the present study, indicating that genetic polymorphisms are the most important factor influencing the metabolism of inorganic arsenic.     

Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in children

We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7-11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18-79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials.     

Biomarkers of exposure: a case study with inorganic arsenic

The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. iAs and its methylated metabolites are primarily excreted in urine within 4-5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trivalent arsenicals are more potent toxicants than pentavalent forms. Several mechanisms of action have been proposed for arsenic-induced toxicity, but a scientific consensus has not been achieved. Biomarkers of exposure may be used to quantify exposure to iAs. The most common biomarker of exposure for iAs is the measurement of total urinary arsenic. However, consumption of seafood containing high concentrations of organic arsenic can confound estimation of iAs exposure. Because these organic species are thought to be relatively nontoxic, their presence in urine may not represent increased risk. Speciation of urinary arsenic into inorganic and organic forms, and even oxidation state, gives a more definitive indication of the exposure to iAs. Questions still remain, however, as to how reliably the measurement of urinary arsenic, either total or speciated, may predict arsenic concentrations at target tissues as well as how this measurement could be used to assess chronic exposures to iAs.     

Metabolism of inorganic arsenic to organoarsenicals in rainbow trout (Salmo gairdneri)

Chemical speciation of arsenic was examined by radioactive tracer and chromatographic techniques applied to muscle, liver, kidney, blood, bile, and urine from rainbow trout (Salmo gairdneri) given an oral dose of ⁷⁴As as arsenic acid. Conversion to organic forms of arsenic was rapid and extensive. The ratio of total organic to inorganic increased with time in all tissues, with the organic arsenic fraction accounting for about 50% at 6 hr and over 80% at 24 hr. An organoarsenic metabolite was shown by thin-layer chromatography to have the same R_f as ethylarsenobetaine, and this compound accounted for the major portion of the total arsenic in all tissues including bile and urine sampled 24–96 hr postdose.     

Nutritional status has marginal influence on the metabolism of inorganic arsenic in pregnant Bangladeshi women

BACKGROUND: The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear. OBJECTIVES: In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water. METHODS: We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry. RESULTS: The median concentration of As in urine was 97 microg/L (range, 5-1,216 microg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation. CONCLUSIONS: In spite of the high As exposure and prevalent malnutrition, overall As methylation in women in early pregnancy was remarkably efficient. The As exposure level had the greatest impact on As methylation among the studied factors.     

Carcinogenic risks of inorganic arsenic in perspective

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.Work presented at the 23rd Congress on Occupational and Environmental Health in the Chemical Industry (Medichem 1995) The Chemical Industry as a Global Citizen - Balancing Risks and Benefits, 19–22 September 1995, Massachusetts Institute of Technology, Cambridge Massachusetts D. M. Byrd, R. Wilson, S. Lai and S. H. Lamm are members of the Inner Mongolia Cooperative Arsenic Project     

中国汉族人口三种谷胱甘肽S-转移酶基因多态性分析

目的：分析中国汉族人口谷胱甘肽S－转移酶（GSTs)基因多态性分布。方法：样本为450名中国汉族人口,采用多重等位基因特异聚合酶链反应（PCR）方法分析GSTM1和GSTT1基因多态性,采用PCR－限制性片段长度多态性方法分析GSTP1＋313核苷酸位点的基因多态性。结果：GSTM1缺失型和GSTT1缺失型基因型频率分别为57％和45％,同时具有GSTM1缺失型和GSTT1缺失型基因型的人个体频率为28．92％;而GSTP1＋313位点G等位基因频率为18．7％,并发现该人群中同时具有3种危险基因型（GSTM1缺失型、GSTT1缺失型和GSTP1＋313A／A）的个体频率为18．04％。GSTs基因型分布不受性别和年龄的影响。结论：中国汉族人口GSTM1、GSTT1和GSTP1基因呈多态性分布,其等位基因和基因型频率不同于其他种族。     

Intra-individual variation in the metabolism of inorganic arsenic

OBJECTIVE: Inorganic arsenic is metabolized to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are excreted in the urine. Previous studies have shown a marked inter-individual variation in the metabolism, but the within-person variation is unknown. Therefore, we determined the variation in the relative amount of urinary arsenic metabolites, i.e., inorganic arsenic, MMA and DMA, over time in women living in an Andean village with elevated arsenic levels in drinking water. METHODS: For our investigation of the individual day-to-day variation, daily spot urine samples were collected (at the same time of the day) for 5 consecutive days by 15 women. For our investigation of the within-day variation, seven women collected all the urine voided over a 72-h period, each voided into a separate container. RESULTS: Repeated measures analysis of variance (ANOVA) revealed no significant day-to-day variation, either in the relative distribution of inorganic arsenic metabolites (inorganic arsenic, MMA and DMA), or in the concentration of the metabolites. However, the percentage of DMA was slightly higher (on average 5.0%; P=0.003) and the percentage of inorganic arsenic lower (on average 5.8%; P=0.001) during the morning/day (03:00-15:00) compared with the evening/night (15:00-03:00). No within-day variation in the percentage of MMA was observed. CONCLUSION: The arsenic methylation efficiency of an individual is remarkably stable over time.     

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50?μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1?μg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.     

山西地区血管紧张素原基因和α-内收蛋白基因多态性与原发性高血压的相关性研究

目的调查山西地区血管紧张素原(angiotensinogen,AGT)和α-内收蛋白(alpha-aduction,ADD1)基因多态性与原发性高血压(essential hypertension,EH)的关系。方法采用病例对照研究,用诱变分离聚合酶链反应(mutagenically separated polymerase chain reactions,MS-PCR)检测山西地区EH患者299例(病例组)和血压正常者218例(对照组)的AGT基因M235T多态性和ADD1基因Gly460Trp多态性。结果病例组AGT基因的TT基因型分布与对照组差异有统计学意义(P<0.001),但病例组T等位基因频率(0.426)与对照组(0.378)相比,差异无统计学意义(P=0.121)。病例组ADD1基因型分布和等位基因频率与对照组相比,差异均无统计学意义(P分别为0.306和0.072)。TT+TT联合基因型患EH的危险度增加(MT+GG:OR=0.410,P=0.041;MT+GT:OR=0.364,P=0.020;MT+TT:OR=0.262,P=0.002)。Logistic回归分析提示,AGT基因的TT基...     

Airborne arsenic and urinary excretion of metabolites of inorganic arsenic among smelter workers

Summary The relationship between airborne concentrations of arsenic and the urinary excretion of inorganic arsenic metabolites (inorganic arsenic + methylarsonic acid + dimethylarsinic acid) have been studied among smelter workers exposed to arsenic trioxide. The urinary concentrations of arsenic metabolites were found to increase steadily during the first day of the working week (after 2–3 d off from work), whereafter they reached a steady state. The concentration in the late evening after a day of exposure was very similar to that in the early morning after. Both were well correlated to the total daily excretion. In the second part of the study, comprising 18 subjects, the first-void morning urine of each participant was collected for 2 to 3 d during the steady-state phase. Total concentration of arsenic in the breathing zones was measured by personal air samplers. Airborne arsenic (8-h values) varied between 1 and 194 g As/m³, and urinary arsenic between 16 and 328 g As/g creatinine. With the urinary arsenic concentrations (mean values of 2–3 d for each subject) plotted against the corresponding airborne arsenic concentrations, the best fit was obtained by a power curve with the equation y = 17 x x^0.56. However, four of the participants were found to excrete far more (105–260%) arsenic in the urine than possibly could have been inhaled, most likely due to oral intake of arsenic via contaminated hands, cigarettes or snuff. If these four were excluded, the best fit was obtained by a straight regression line with the slope 2.0 and the intercept 29 g As/g creatinine (coefficient of correlation 0.92; P < 0.001).     

凉茶中总砷和无机砷的测定

目的:探讨氢化物发生原子荧光光谱法测定凉茶中的总砷和无机砷含量.方法:凉茶经硝酸和高氯酸消化后,用硫脲抗坏血酸使五价砷还原为三价,再与硼氢化钾反应生成砷化氢气体,载入原子荧光光谱仪测定总砷;20%盐酸溶液中无机砷被碘化钾-硫脲还原为三价的砷,与硼氢化钾反应生成砷化氢气体与基底分离,载人原子化器测定无机砷.结果:总砷在0～40.000 ng/mI的范围内线性良好,相关系数为0.9999,检出限为0.005μg/L,RSD范围为0.86%～3.39%,回收率范围为94.2%%～109.2%;无机砷在0～50.000 ng/ml的范围内线性良好,相关系数为0.9999,检出限为0.024μg/L,RSD范围为1.88%～8.26%,回收率范围为81.0%～101.4%.所检测凉茶的总砷及无机砷含量均小于0.2 mg/L.结论:该方法具有较高的准确度和精密度,检出限低,操作简单,适宜于凉茶中总砷和无机砷的测定.所检广州市售凉茶总砷及无机砷含量较低.     

Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.     

Genotoxic effects in a population of nurses handling antineoplastic drugs, and relationship with genetic polymorphisms in DNA repair enzymes

BACKGROUND: Concern about the genotoxic risk associated with chronic handling of antineoplastic drugs has increased, and usual safety practices may not avoid exposure. METHODS: Comet assay and MN test were performed on 30 oncology nurses and 22 controls. Genetic polymorphisms of XRCC1, XRCC3, and APE1 genes were determined by PCR-RFLP. RESULTS: Data obtained showed increased cytogenetic and DNA damage in the exposed group, although statistical significance was only reached in the comet assay. Significant differences in TL were observed for carriers of the variant alleles of every gene analyzed. However, no significant effect was detected in the MN test. CONCLUSIONS: Evidence that the present handling practices of antineoplastic drugs in some Portuguese hospitals are not enough to prevent exposure are provided. Present data suggest that genetic polymorphisms in the studied DNA repair enzymes may influence the individual susceptibility to DNA damage related to chronic handling of antineoplastic drugs.