Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde.

OBJECTIVES: Structural chromosomal aberrations in blood lymphocytes represent a biomarker for cellular damage caused by genotoxic carcinogens and are an indicator of increased cancer risk. We evaluated the association between frequencies of total chromosomal aberrations, chromatid- and chromosome-type aberrations, and occupational exposures to volatile anesthetics, antineoplastic agents, and formaldehyde among 601 medical professionals. METHODS: Chromosomal damage among exposed individuals and unexposed controls was determined by conventional cytogenetic analysis. We used binary logistic regression to evaluate the effects of workplace exposures and major confounders on chromosomal damage. RESULTS: Significantly higher frequencies of total chromosomal, chromatid-type and chromosome-type aberrations were observed among subjects occupationally exposed to volatile anesthetics, antineoplastic agents, and formaldehyde compared to age- and sex-matched controls (P<0.0001). The risk of an increased frequency of chromosomal aberrations was associated with exposure to anesthetics [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 2.7-5.8], cytostatics (OR 2.7, 95% CI 1.9-3.9), and formaldehyde (OR 1.7, 95% CI 1.1-2.7). No other covariate contributed significantly to the model. Chromatid- and chromosome-type aberrations were associated with exposure to anesthetics and cytostatics without any contribution of other variables. Stratified data analysis showed the risk of increased chromosomal aberrations among non-smoking female nurses and physicians exposed to anesthetics, cytostatics and, partially, formaldehyde. Chromatid and chromosome exchanges were significantly higher in the exposed groups than among controls. CONCLUSION: Our findings indicate that the presence of genotoxic compounds in operating rooms, oncological units, and pathological departments results in a significant increase of chromosomal damage (impair of chromosomal integrity) among medical workers employed in these facilities.

Evaluating chromosomal damage in workers exposed to hexavalent chromium and the modulating role of polymorphisms of DNA repair genes.

PURPOSE: Welders have been chronically exposed to hexavalent chromium with potential consequences on chromosomal integrity. Our study is focused on the extent of any such chromosomal aberrations with respect to chromium levels in the blood of welders as well as on the tentative modulating role of polymorphisms in DNA repair genes XPD Lys751Gln, XPG Asn114His, XPC Lys939Gln, hOGG1 Ser326Cys and XRCC1 Arg399Gln on chromosomal damage. METHODS: The study was conducted on 144 individuals consisting of 73 welders exposed to chromium for 10.2 ± 1.67 years and 71 control individuals without known exposures. Chromosomal aberrations, their chromatid-type and chromosome-type aberrations were detected by conventional cytogenetic analysis. XPD, XPG, XPC, hOGG1 and XRCC1 gene polymorphisms were assayed for by Taqman SNP genotyping assay ("Assay-by-Demand") using Real-Time allelic discrimination on AB 7500 equipment. Chromium concentration in the blood was determined by atomic absorption spectrophotometry. RESULTS: The level of chromium in the blood of welders ranged between 0.032 and 0.182 µmol l(-1) and was significantly higher than that in controls (0.07 ± 0.04 µmol l(-1) vs. 0.03 ± 0.007 µmol l(-1)). Parameters of chromosomal damage were similar in both the exposed and the control individuals (1.89% vs. 1.70% for total chromosomal aberrations, 0.97% vs. 0.88% for chromosome-type and 0.92% vs. 0.80% for chromatid-type, respectively). Chromatid-type of aberrations positively correlated with the level of chromium in the blood (r = 0.28; P = 0.02). Significantly higher total chromosomal aberrations were detected in individuals with homozygous variant polymorphism in XRCC1 Arg399Gln gene as compared to those with heterozygous and homozygous wild-type genotypes (2.20, 1.89 and 1.48%, respectively; P = 0.01). A similar tendency was found for chromatid-type aberrations (1.30% for homozygous variant genotype bearers, 0.94% for those with heterozygous genotype and 0.75% for carriers of homozygous wild-type genotype, respectively; P = 0.04). CONCLUSIONS: Although no apparent increase in chromosomal damage was recorded in chromium-exposed welders in comparison with controls, genetic make-up in DNA repair genes may increase susceptibility toward adverse effect of chromium.

Human lung cancer and hexavalent chromium exposure.

OBJECTIVE: Workers chronically exposed to hexavalent chromium have higher incidence of lung cancer. Our study investigates incidence of lung cancer types, age at onset of the disease and survival time among chromium exposed workers (smelters, tapers, crane operators) in comparison to non-exposed persons. METHODS: 64 chromium exposed workers and 104 male controls with diagnosed lung cancer were analysed. The average exposure time among workers was 16.71 +/- 10.02 (S.D.) years (range 1- 41 years). RESULTS: Chromium exposure significantly decreases the age at the onset of the disease by 3.51 years (62.20 +/- 9.08 years in exposed group and 65.71 +/- 10.50 years in control; P=0.018). Small cell lung carcinoma (SCLC) forms 25.0 % of all cases in chromium exposed workers and 16.34% in non exposed individuals. No correlation was found between the age at the diseases onset and time of exposure. The mean survival time in exposed group was 9.03 +/- 12.73 month, in control 12.14 +/- 21.94 month, but this difference was not significant (P=0.473). CONCLUSION: Occupational exposure to chromium was identified as an important risk factor of lung cancer, decreasing the age at the diseases onset. Higher percentage of SCLC was found in chromium exposed individuals.

Comparison of chromosomal aberrations frequency and polymorphism of GSTs genes in workers occupationally exposed to cytostatics or anaesthetics.

Authors compared the incidence of chromosomal aberrations (CAs) of workers occupationally exposed to cytostatics (group EXP1) or anaesthetics (group EXP2) in relationship to polymorphism of GSTM1, GSTP1 and GSTT1 genes. The cytogenetic analysis for chromosomal aberrations frequency and for polymorphisms of genes the PCR and PCR-RFLP method were used. Statistically higher frequency of total CAs was detected in both exposed groups: group EXP1 1.90±1.34%; Mann-Whitney U-test, p=0.001; group EXP2 2.53±1.46%, p=0.0008) as compared to control (1.26±0.93%). In group EXP2 was detected statistically higher frequency of aberrations CSA-type as compared to CTA-type. In xenobiotic metabolizing genes for GST higher frequency of total CAs and constituent types chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) of genes GSTM1 and GSTT1 with null genotype was detected. Statistically significant difference was detected only in CSA-type of aberrations in GSTT1 gene. In gene GSTP1 was not detected any difference in frequency of aberrations in presence of the variant allele. Presented results point out importance of individual susceptibility in evaluation of genotoxic agents of anaesthetics or cytostatics.