Cytogenetic monitoring of industrial populations potentially exposed to genotoxic chemicals and of control populations

Currently the most applied technique for monitoring biological effects of exposure to genotoxic chemicals in industrial workers is the measurement of chromosome aberrations in peripheral blood lymphocytes. In the Shell petrochemical complex in The Netherlands cytogenetic monitoring studies have been carried out from 1976 till 1981 inclusive, in workers potentially exposed to a variety of genotoxic chemicals, i.e. vinyl chloride, ethylene oxide, benzene, epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were well below the occupational exposure limits. Results of these studies indicate that no biologically significant increase in the frequencies of chromosome aberrations in the exposed populations occurred compared with control populations. Our experience with this methodology has shown that the results of chromosome analyses are difficult to interpret, due to the variable and high background levels of chromosome aberrations in control populations and in individuals. It is concluded that the method is not sufficiently sensitive for routine monitoring of cytogenetic effects in workers exposed to the low levels of genotoxic compounds.     

Association of HSP70 and genotoxic damage in lymphocytes of workers exposed to coke-oven emission

Heat shock proteins (Hsps) have been reported to protect cells, tissues, and organisms against damage from a wide variety of stressful stimuli. Whether they protect against deoxyribonucleic acid (DNA) damage in individuals exposed to environmental stresses and chemical carcinogens is unknown. In the study, we investigated the association between Hsp70 levels (the most abundant mammalian Hsp) and genotoxic damage in lymphocytes of workers exposed to coke-oven emission using Western dot blot and 2 DNA damage assays, the comet assay and the micronucleus test. The data show that there is a significant increase in Hsp70 levels, DNA damage score, and micronucleus rates in lymphocytes of workers exposed to coke-oven emission as compared with the control subjects. Furthermore, there was a significant negative correlation of Hsp70 levels with DNA damage scores in the comet assay (r = -0.663, P < 0.01) and with micronucleus rates (r = -0.461, P < 0.01) in the exposed group. In the control group, there was also a light negative correlation between Hsp70 with DNA damage and micronuclei rate (r = -0.236 and r = 0.242, respectively), but it did not reach a statistically significant level (P > 0.05). Our results show that individuals who had high Hsp70 levels generally showed lower genotoxic damage than others. These results suggest a role of Hsp70 in the protection of DNA from genotoxic damage induced by coke-oven emission.     

Theory and practice of primary cancer prevention

The primary aim of cancer prevention is to stop carcinogens from entering the body. Since the low doses involved in carcinogenesis do not cause true toxicological effects, usual toxicological analytic methods do not allow the detection of the early effects of carcinogens. Exposure to chemical carcinogens causes damage to nuclear chromatin, the most vulnerable part of the cell, by inducing DNA damage, chromosomal abnormalities and mutations, which foreshadow the danger of cancer development. In such cases intervention is possible in two ways. On the one hand, we attempt to remove the causative agent from the environment, while on the other we aid the elimination of somatic mutations. The latter is called active prevention; the introduction of substances into the body that can help the elimination of defective cells (apoptosis induction) or stop processes responsible for elongation errors (i.e. with antioxidants). Concerning our own studies, we present the results of 25 years of research on the genotoxicological characteristics of workers exposed to various chemicals, which show that active prevention can in fact be effective in conjunction with information on specific biomarkers. We present in detail the genotoxic changes found in hospital nurses who routinely administer intravenous cytostatic therapy, and the relationship of these changes to their immunotoxic and clinical laboratory parameters. Genotoxic substances decrease the oxidative burst and natural killer (NK) cell activity, which may explain the immunosuppressive effects of occupational exposures. We also present the detailed results of a follow-up study involving two groups of industrial workers. We monitored the status of workers involved in benzene production for 15 years and of asphalt industry workers for 8 years. In both studies we concluded that genotoxic effects can be decreased by ensuring appropriate working conditions, while a temporary lapse in these conditions or accidental changes lead to increases in genotoxic parameters. Since genotoxic effects develop over an extended period (4-5 months), they are independent of hygienic conditions at any single inspection and, thus, their detection also offers a way to ascertain true exposure levels. Our studies also show a connection between genotoxic effects and immune function, which is adversely affected not only by occupational exposures, but also by medications and smoking. From our results with workers in the oil and asphalt industries, we concluded that the levels of chromosomal aberrations (CAs) and sister chromatid exchange (SCE) increase in proportion to exposure levels and decrease with a certain delay following the attenuation of the exposure. We could not detect an increased frequency of any chronic disease in industrial workers. The increased numbers of iron deficiency anemia and thyroid disease in nurses providing cytostatic therapy was, however, related to their occupational exposure.     

Cytogenetic damage in workers from a coal-fired power plant

The aim of this study was to investigate the genotoxic risk to workers occupationally exposed to coal combustion products in Afsin-Elbistan A power plant, located in south-eastern Turkey. We analysed chromosomal aberrations (CAs), polyploidy, sister-chromatid exchanges (SCEs), and micronuclei (MN) in 48 male workers without a history of smoking, tobacco chewing, or alcohol consumption. The results were compared with a control group of 30 healthy male individuals without exposure to any known genotoxic agents. The mean frequencies of CA, polyploidy, SCEs (P<0.01), and MN (P<0.05) were significantly higher in workers than in the control group, by the Mann-Whitney U-test. Spearman's rho correlation analysis revealed a significant increase in the frequency of CA and MN with increasing years of exposure (P<0.05). However, there was no significant effect of age on the cytogenetic markers analysed in both groups (P>0.05). The data obtained from this study clearly showed chromosomal hazard in the peripheral lymphocytes of workers exposed to coal combustion products in Afsin-Elbistan A power plant for several years. This cytogenetic damage might be attributed to the cumulative effects of several substances due to chemical complexity of the coal ash and gaseous emissions rather than a specific substance.     

Leather tanning workers: chromosomal aberrations in peripheral lymphocytes and micronuclei in exfoliated cells in urine

A cytogenetic study was performed on workers of a leather tanning industry. Two different approaches for the biological monitoring of the individuals were used: chromosomal aberration analysis in peripheral lymphocytes and the frequency of micronucleated cells exfoliated in urine samples. 26 men working in the sections considered to present a greater risk were included in the study. Controls were 20 men that were not exposed to chemicals. The percentage of abnormal cells was higher in workers than in controls. Smokers showed higher values of chromosome breaks than non-smokers in both groups. These differences were not statistically significant. The percentage of cells with chromatid and chromosome gaps in workers and controls was different (p less than 0.01). A slight but not significant increase in the mean percentage of micronuclei was observed in the exposed group. We conclude that exposure to chemicals during leather tanning did not produce genotoxic effects measured by chromosomal aberrations in peripheral lymphocytes and micronuclei in urine in this group of workers.     

Genotoxic effects of occupational exposure to lead and cadmium

This study was designed to assess genotoxic damage in somatic cells of workers in a Polish battery plant after high-level occupational exposure to lead (Pb) and cadmium (Cd), by use of the following techniques: the micronucleus (MN) assay, combined with in situ fluorescence hybridization (FISH) with pan-centromeric probes, analysis of sister chromatid exchanges (SCEs), and the comet assay. Blood samples from 44 workers exposed to lead, 22 exposed to cadmium, and 52 unexposed persons were used for SCE and MN analysis with 5'-bromodeoxyuridine (BrdU) or cytokinesis block, respectively. In parallel, the comet assay was performed with blood samples from the same persons for detection of DNA damage, including single-strand breaks (SSB) and alkali-labile sites (ALS). In workers exposed mostly to lead, blood Pb concentrations ranged from 282 to 655 microg/l, while the range in the controls was from 17 to 180 microg/l. Cd concentration in lead-exposed workers fell in the same range as for the controls. In workers exposed mainly to cadmium, blood Cd levels varied from 5.4 to 30.8 microg/l, with respective values for controls within the range of 0.2-5.7 microg/l. Pb concentrations were similar as for the controls. The incidence of MN in peripheral lymphocytes from workers exposed to Pb and Cd was over twice as high as in the controls (P<0.01). Using a combination of conventional scoring of MN and FISH with pan-centromeric probes, we assessed that this increase may have been due to clastogenic as well as aneugenic effects. In Cd- and Pb-exposed workers, the frequency of SCEs as well as the incidence of leukocytes with DNA fragmentation in lymphocytes were slightly, but significantly increased ( P<0.05) as compared with controls. After a 3h incubation of the cells to allow for DNA repair, a clear decrease was found in the level of DNA damage in the controls as well as in the exposed workers. No significant influence of smoking on genotoxic damage could be detected in metal-exposed cohorts. Our findings indicate that lead and cadmium induce clastogenic as well as aneugenic effects in peripheral lymphocytes, indicating a potential health risk for working populations with significant exposures to these heavy metals.     

Mini-and microsatellite mutations in children from Chernobyl accident cleanup workers

Knowledge about possible genotoxic effects of low-dose radiation on the human germline is limited and relies primarily on extrapolations from high-dose exposures. To test whether ionizing radiation can cause paternal genetic mutations that are transmitted to offspring, we enrolled families of 88 Chernobyl cleanup workers exposed to ionizing radiation. We analyzed DNA isolated from lymphocytes for mutations via DNA blotting with the multi-locus minisatellite probes 33.6 and 33.15 and via PCR in a panel of six tetranucleotide repeats. Children conceived before and children conceived after their father's exposure showed no statistically significant differences in mutation frequencies. We saw an increase in germline microsatellite mutations after radiation exposure that was not statistically significant. We found no dependence of mutation rate on increasing exposure. A novel finding was that the tetranucleotide marker D7S1482 demonstrated germline hypermutability. In conclusion, our results do not support an increased level of germline minisatellite mutations but suggest a modest increase in germline mutations in tetranucleotide repeats. Small sample size, however, limited statistical power.     

Genetic monitoring of aluminum workers exposed to coal tar pitch volatiles

A group of 50 workers exposed to coal tar pitch volatiles (CTPV) in an aluminum reduction plant and a group of 50 non-exposed workers were selected to evaluate the genotoxic effects of CTPV exposure. A battery of tests was performed on 3 different body fluids; urine, blood and semen. Urine samples were evaluated for mutagenic constituents using the Ames/Salmonella assay. Cultured lymphocytes from blood samples were used to perform cytogenetic analysis. Semen samples were used to measure sperm count, percent abnormal sperm morphology and frequency of sperm carrying double fluorescent bodies (2-F). 14 of 28 (50%) exposed workers and 7 of 36 (19.4%) non-exposed workers had mutagenic urine. This difference was significant (p less than 0.01). Among the non-smokers a significantly higher percentage of workers who were exposed had positive urine (36%) compared to the non-exposed workers (5%) (p less than 0.05). Among the exposed group, more mechanics had mutagenic urine than did other types of workers. Overall chromosome aberration rates were similar in both exposed and non-exposed workers. Among exposed workers a significant inverse correlation (p less than 0.05) between age and chromatid aberration rate was observed. Results of semen analysis failed to detect differences between exposed and non-exposed workers. Results of these tests lend support to a battery approach to genetic monitoring and suggest a link between exposure to CTPV and genotoxic effects. Detection of exposure to mutagens at an early time offers an opportunity for disease prevention by the reduction of exposure.     

No increase in micronuclei frequency in cultured blood lymphocytes from a group of filling station attendants

Service station attendants are workers that are definitely exposed to petroleum derivatives. Taking into account that this exposure has been considered to possess genotoxic risk, here we present data on the biomonitoring of a group of 50 service station workers and 43 controls. Micronuclei (MN) from peripheral blood lymphocytes has been considered as the genetic endpoint to be studied and, in addition, data on the concentration of aromatic hydrocarbons at the workplace, urinary metabolites and differential white blood cell count have also been analysed. The results obtained indicate no significant differences between petrol station attendants and controls, when the effects of petrol exposure were investigated by differential white blood cell count and analysis of MN frequencies in phytohaemagglutinin-stimulated lymphocytes. Regarding the urinary metabolites, a significant increase in the phenol level was found in the exposed workers.     

Chromosomal aberrations in humans as genetic endpoints to assess the impact of pollution

The chromosomal aberration assay with peripheral blood lymphocytes has been used routinely during the last three decades to survey exposure of humans to various genotoxic agents. A large number of biomonitoring studies are based on this genetic endpoint. A great deal of data exists on occupational, life-style or medical exposure situations but less evidence of the validity of the assay is available with regards to environmental exposure. In the present paper we report our investigations on the impact of pollution in two different populations using chromosomal aberrations in human peripheral blood lymphocytes as a biomarker of chronic exposure to heavy metals and dioxins/furans for a long period and as a biomarker of acute exposure to accidentally released vinyl chloride in the air. In order to study genotoxic effects (chromosomal aberrations) of heavy metals and dioxins/furans, 52 exposed individuals from a polluted area were compared to 51 matched controls from a distant non-industrialized area. A statistically significant increase was observed in the frequency of chromosomal aberrations in peripheral blood lymphocytes from the exposed population (1.90% aberrant cells vs. 1.11% for the controls). In the case of the vinyl chloride accident, chromosomal aberrations were analyzed in peripheral blood lymphocytes from 29 potentially exposed and 29 non-exposed individuals (matched controls). The exposed group showed a statistically significant increase in the frequency of aberrant cells (1.47% vs. 1.07% for the controls).     

Micronucleus frequencies in workers exposed to lead, zinc, and cadmium

Micronuclei (MN) in blood lymphocytes were determined in 31 male workers occupationally exposed to lead (Pb), zinc (Zn), and cadmium (Cd) and 20 control workers matched for age and smoking habits. Exposed workers have higher MN mean values than control workers (p<0.01). In exposed workers, blood Pb concentrations were also significantly higher than in control workers (p<0.001), but the mean concentrations of Zn and Cd in the blood were not statistically significant compared to the controls (p>0.05). These results suggest that lead may be genotoxic and the human lymphocyte micronucleus test can be used to assess genotoxic effects that result from occupational exposures.     

The frequency of illegitimate TCRbeta/gamma gene recombination in human lymphocytes: influence of age, environmental exposure and cytostatic treatment, and correlation with frequencies of t(14;18) and hprt mutation.

Chromosome translocations in lymphoid malignancies often involve V(D)J recombinase mediated events giving rise to aberrant T-cell receptor (TCR) and immunoglobulin genes, which have been suggested to be useful as markers of genomic instability, genotoxic exposure and cancer risk. Illegitimate rearrangements involving the TCRbeta/gamma loci on chromosome 7 create TCRbeta/gamma hybrid genes which occur at low frequency in peripheral blood lymphocytes (PBLs) of normal healthy individuals. To evaluate the utility of this marker, we studied the possible effects of age and genotoxic exposures on the TCRbeta/gamma gene variant frequency (VF), and compared the frequencies of hypoxanthine guanine phosphoribosyl transferase (hprt) mutation, hprt exon 2/3 deletion, t(14;18) and TCRbeta/gamma gene rearrangements in cells from the same donors. The TCRbeta/gamma VF ranged five-fold among 16 middle aged blood donors with a mean of 0.74+/-0.29/10(5) PBLs, which is consistent with our previous estimate in healthy subjects. The TCRbeta/gamma VF was found to increase from birth until early adult life, and then to decrease with increasing age. Four testis cancer patients, who 6 years earlier had been treated with etoposide and other cytostatic drugs, showed TCRbeta/gamma VF similar to that in healthy controls. No increase of the TCRbeta/gamma VF was found among non-smoking PAH-exposed aluminum smelter workers compared to non-smoking controls. Smoking smelter workers showed decreased TCRbeta/gamma VF compared to non-smoking workers and controls, but in a follow-up study 2 years later the difference was no longer statistically significant, although the smoking smelter workers still showed a lower TCRbeta/gamma VF than the controls. No correlation was obtained between the TCRbeta/gamma VF and the t(14;18) or hprt mutant frequency (MF) in a group of healthy individuals. However, there was a statistically significant correlation between the TCRbeta/gamma VF and the hprt exon 2/3 deletion frequency in PBL DNA from the same donors. These results show that the TCRbeta/gamma VF in healthy individuals changes with age and correlates with the frequency of hprt exon 2/3 deletion, another marker of aberrant V(D)J recombination in T-cells. However, no effect of smoking or present or previous exposure to genotoxic agents on TCRbeta/gamma VF was observed in this study. Thus, further studies are needed to prove the utility of TCRbeta/gamma gene rearrangement as a marker of genotoxic exposure.     

Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay

A follow-up study was carried out 4 years after an initial evaluation of the micronucleus frequency in 10 healthy individuals who had been occupationally exposed to antineoplastic drugs in a Brazilian hospital. Upon the first evaluation, these 10 exposed individuals were compared with 10 non-exposed individuals matched for age, sex and smoking habits; the results revealed that the frequency of micronucleated lymphocytes in individuals exposed to antineoplastic drugs was significantly higher (P=0.038) than in controls. The frequency of dicentric bridges was also increased, although not significantly (P=0.0545). After the first analysis, the workers handling antineoplastic drugs were advised to modify their work schedule to limit exposure, and the number of workers in the group was increased from 10 to 12 individuals. In the follow-up study, 12 individuals from the same work area were assessed. In addition to micronucleus frequency, alkaline single cell gel electrophoresis was also used to monitor genetic hazard. This exposed group was compared to 12 non-exposed workers from the same hospital, matched for age, sex and smoking habits. In the follow-up study, no statistical difference was found between exposed workers and controls in terms of micronucleus and dicentric bridge frequency with the Mann--Whitney U-test (P=0.129 and 0.373, respectively). However, the mean value of SCGE analysis was significantly higher in the exposed group than in the controls (P=0.0006). Although the micronucleus analysis seems to be less sensitive to assess DNA damage, it detects chromosome aberrations and not just repairable DNA breakage and alkali-labile sites. Combination of the alkaline single cell gel electrophoresis and cytokinesis blocked micronucleus assay appears to be commendable to monitor populations chronically exposed to genotoxic agents.     

Study of the cytogenetic effects of occupational exposure to pesticides on sanitation workers in Belo Horizonte, Brazil

Sanitation workers handling pesticides in the control of disease vectors constitute an occupationally exposed population to genotoxic substances. The aim of the present study was to investigate the relation between the occupational exposure to various pesticides and the presence of cytogenetic damage. Fifty-nine men were selected (29 sanitation workers and 30 control individuals) with ages varying between 18-57 years who lived and worked in the same area in Belo Horizonte (Brazil). The following parameters were determined for all individuals using the cytokinesis-block micronucleus (MN) assay in peripheral blood lymphocytes: MN/1000 binucleated cells (BC), BC with MN (BCMN)/1000 BC, nucleoplasmic bridges (NB)/1000 BC, apoptotic and necrotic cells/500 cells and nuclear division index. The analysis of covariance showed significantly higher (p < 0.05) mean frequencies of MN (15.81 +/- 1.31 vs 4.71 +/- 0.42), BCMN (15.10 +/- 1.22 vs 4.62 +/- 0.44), NB (4.59 +/- 0.76 vs 1.00 +/- 0.34), and necrotic cells (12.07 +/- 1.45 vs 5.17 +/- 0.70) in the exposed group when compared to the control group. There was no significant difference in the apoptotic cell frequency between the two groups, while the nuclear division index was significantly lower (1.49 +/- 0.02 vs 1.61 +/- 0.02) in the control group. Neither the time of exposure nor the smoking or alcohol drinking habit influenced the cytogenetic parameters examined. According to these results, occupational exposure to pesticides induced genotoxic and cytotoxic effects in sanitation workers.     

Evaluation of genotoxicity in a group of workers from a petroleum refinery aromatics plant

Petroleum refinery workers are potentially exposed to a wide range of petroleum-derived hydrocarbons and chemical substances used in the manufacturing of petroleum derivatives. Benzene, toluene and xylene (BTX) are produced by distillation in the aromatics units and used as raw materials for petrol and petrochemical products. The aim of this study was to evaluate the genotoxic effects of occupational exposure to BTX in a petroleum refinery in the North of Portugal. The exposed group consisted of 48 workers from the aromatics plant and the control group consisted of 30 persons matched for various confounding factors. Chromosome aberrations (CA), micronuclei (MN), and DNA damage (evaluated by means of the comet assay) were measured in peripheral blood leukocytes. t,t-Muconic acid (t,t-MA), hippuric acid (HA) and methylhippuric acid (MHA) concentrations were measured in urine samples collected at the end of the workshift. The results suggest that occupational exposure to toluene and xylene is very low. A statistically significant increase in t,t-MA excretion was found in the exposed group although t,t-MA levels were found to be lower than the biological exposure index (BEI). Significant increases were found for CA, MN and comet tail length (TL) in the exposed group (p<0.05). No association was found between tobacco smoking and the effect biomarkers analysed. A positive association was found between CA and MN with age in the control group (p<0.05).     

No significant increase in sister-chromatid exchanges in cultured blood lymphocytes from workers in a large oil refinery

In order to assess the potential genotoxic effects of occupational exposure to petrochemicals, the incidence of sister-chromatid exchanges (SCE) in cultured lymphocytes was studied. Blood samples were taken from 233 individuals (184 exposed and 49 worksite controls) in an oil refinery and from 47 community control persons. The data showed a non-significant elevation of SCE frequency in occupationally exposed workers when compared to non-exposed individuals. The mean SCE frequency per cell ranged from 7.55 ± 0.55 in blood of lube oil blending and canning (LOBC) workers to 9.13 ± 0.71 in catalytic cracking and water treatment (CCWT) workers. The control values were 6.2 ± 0.67 and 7.21 ± 0.45 in the community and worksite individuals, respectively. Furthermore, the SCE frequencies were influenced neither by age nor by smoking.     

Effect of sulphur dioxide exposure on human chromosomes

The genotoxic effects of an average concentration of 41.7 mg/m³ of SO₂ exposure on 42 workers of a fertilizer factory were investigated. Mitotic index (MI), chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs) and satellite associations (SA) were observed. In SO₂-exposed workers, a higher mitotic index (7.09) was recorded in comparison to controls (4.34). The MI, however, declined with duration of exposure. Satellite associations showed a two-fold increase (17.1) as compared to controls (8.11). Among chromosomes, D-G group associations were the highest (7.43%), while 3D type associations were the lowest (0.4%). There was a significant difference (p < 0.05) in the mean frequency of CAs per cell in the exposed workers (3.262%) and the controls (0.833%). The mean frequency of SCEs per cell increased from 3.32 ± 0.1 in controls to 7.72 ± 0.19 in the exposed group. The difference was significant (p < 0.05). In smokers, alcoholics and smoker-alcoholics, the frequency of CAs and SCEs per cell was significantly higher than the non-smokers and non-alcoholics, both in the controls and the SO₂-exposed workers and showed a correlation with the duration of exposure. SO₂ is therefore a clastogenic and genotoxic agent for which necessary precautions must be taken.     

Multiple biomarkers study in painters in a shipyard in Korea

Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P<0.001). Paint use, irrespective of the type of paints, and smoking (yes/no) were positively associated with urinary 1-OHPG levels, whereas green tea consumption (yes/no) was negatively associated with the 1-OHPG levels. No significant effect in the 1-OHPG levels were observed for the GSTM1 and GSTT1 genotypes. Aromatic-DNA adduct levels tended to be higher in coal tar paint users (P = 0.06) and painters (P = 0.07) compared to on-site controls. No differences in adduct levels were observed, between the two groups of painters, and the combined group showed greater adduct levels than on-site controls (P = 0.05). GPA mutation frequencies measured in 55 individuals with MN heterozygote genotypes were not significantly different among the three exposure groups, and no correlation was observed between urinary 1-OHPG levels and aromatic-DNA adducts or GPA mutation frequency. These results suggest that painters in the shipyard were exposed to significant amounts of PAHs and possibly to other genotoxic aromatic compounds, and that urinary 1-OHPG may be a potential biomarker of PAH exposure in this population.     

Characterization of chemically exposed groups by immunotoxicological methods

At the National Institute of Chemical Safety we have surveyed the immunological status of donors from the oil industry, health services, and metallurgy exposed to different immunotoxic compounds. Their data were compared to those of healthy, non-exposed controls. Our aim was to study the relationship between immunotoxic exposure and immune function, and to establish a system of immunological parameters by which chemical exposure can be specifically monitored. Subpopulations and activation of lymphocytes was measured by flow cytometry, using immunophenotyping of peripheral blood lymphocytes. In the groups exposed to immunotoxic compounds we found an increase in helper, and a decrease in cytotoxic T lymphocytes, leading to a shift in Th/Tc ratios. These phenomena are not substance specific, but relate to chemical exposure. The lymphocytes of exposed groups showed a higher proportion of activated cells, but there was a difference in the expressed activation markers. Our results suggest that characterizing lymphocyte subpopulations and activation markers on PBL of donors is a useful tool in tracking environmental immunotoxic effects.     

Occupational exposure to genotoxic agents.

Millions of workers in the United States are potentially exposed each year to hazardous chemicals, dusts, or fibers in occupational settings. Some of these agents are genotoxic and may cause genetic alterations in the somatic or germ cells of exposed workers. Such alterations, if they occur in proto-oncogenes or tumor suppressor genes, which are involved in controlling cell growth or differentiation, may lead to the development of cancer. Genetic alterations in germ cells may also lead to reproductive failure or genetic disorders in subsequent generations. It has been estimated that occupational exposure accounts for 4% of all human cancers and up to 30% of cancer among blue-collar workers. Approximately 20,000 cancer deaths each year are attributable to occupational exposure in the United States. Occupational cancer and reproductive abnormalities have been listed on the National Occupational Research Agenda master list of research priorities as major occupational diseases and injuries.