Coke oven workers study: the effect of exposure and GSTM1 and NAT2 genotypes on DNA adduct levels in white blood cells and lymphocytes as determined by 32P-postlabelling.

The DNA adduct levels in total white blood cells (WBC) and lymphocytes (LYM) isolated from the blood of the same individuals were evaluated using the 32P-postlabelling assay for bulky aromatic adducts. In this study, 68 male coke oven workers and 56 machines workers as a matched control were enrolled. Personal monitors were used to evaluate exposure to eight carcinogenic PAHs, including B[alpha]P, during an 8-h working shift. The exposure among coke even workers ranged widely from 0.6 to 547 micrograms/m3 and from 2 to 62,107 ng/m3, for carcinogenic PAHs and B[alpha]P, respectively. The respective values in controls were from 0.07-1.64 microgram/m3 and from 1-63 ng/m3. A significant correlation between WBC- and LYM-DNA adduct levels was found (r = 0.591, P < 0.001). DNA adduct levels in both WBC and LYM were significantly elevated in coke oven workers as compared with controls, but adduct levels were generally low (WBC: medians 2.61 vs. 1.83 LYM: 2.47 vs. 1.65 adducts/10(8) nucleotides). LYM-DNA adduct levels were significantly higher for smokers as compared with nonsmokers in both the exposed and control groups. No such differences in WBC-DNA adduct levels were observed. Positive significant correlations were found at the individual level between DNA adducts in both cell types and carcinogenic PAHs and/or B[alpha]P in the inhaled air (r = 0.38-0.45, P < 0.001). A significant correlation at the individual level between LYM-DNA adducts and urinary cotinine was also observed (r = 0.37, P < 0.001). No differences in DNA adduct levels could be attributed to GSTM1 or NAT2 genotype in either group. Nor was there any clear association of DNA adduct levels with combined GSTM1/NAT2 genotypes. The effect of personal exposure to carcinogenic PAHs on DNA adduct levels in both cell types was also investigated using a logistic regression model with adjustment for possible modulating effect of confounders (smoking, GSTM1, NAT2, age, plasma levels of vitamins A and E, body mass index and diet). The results showed that coke oven workers had a significantly (P < 0.05) increased adjusted Odds Ratio (OR = 4.2 and 3.9 for WBC and LYM-DNA adducts) for occurrence of higher DNA adduct levels as compared to controls. The results also showed that the relative risk of an increased prevalence of 'abnormal' values of DNA adduct levels was exposure-dose related. The influence of confounding variables was found not to be significant in this study of relatively limited size. In spite of this, the results suggest that the DNA adduct levels in LYM seem to be affected by smoking (OR = 1.8 for smokers) and are modulated by the influence of NAT2 genotypes (OR = 1.6 for slow acetylators). Our findings indicate that both cell types are generally suitable to monitor occupational exposure to PAHs, and the results suggest that coke oven workers, smoking individuals and slow acetylators sustain more genetic damage in their LYM-DNA from exposure to carcinogenic PAHs than individuals without these actors.

[1]  J A Swenberg,et al.  Dose-response relationships for carcinogens. , 1995, Toxicology letters.

[2]  K. Vähäkangas,et al.  Assessment of PAH-exposure among coke oven workers. , 1992, Pharmacogenetics (London).

[3]  P. Strickland,et al.  Correlation between PAH airborne concentration and PAH-DNA adducts levels in coke-oven workers , 1993, International archives of occupational and environmental health.

[4]  C. Harris,et al.  Determination of polycyclic aromatic hydrocarbons in the urine, benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amounts of polycyclic aromatic hydrocarbons in the work atmosphere. , 1986, Cancer research.

[5]  P. S. Nielsen,et al.  Environmental air pollution and DNA adducts in Copenhagen bus drivers--effect of GSTM1 and NAT2 genotypes on adduct levels. , 1996, Carcinogenesis.

[6]  A. Weston,et al.  Human DNA adduct measurements: state of the art. , 1996, Environmental health perspectives.

[7]  C. Harris,et al.  Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Bleyl,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs vol. 1 to 42. Supplement 7. 440 Seiten. International Agency for Research on Cancer, Lyon 1987. Preis: 65, – s.Fr , 1989 .

[9]  F. V. van Schooten,et al.  Determination of benzo[a]pyrene diol epoxide-DNA adducts in white blood cell DNA from coke-oven workers: the impact of smoking. , 1990, Journal of the National Cancer Institute.

[10]  Langone Jj,et al.  Radioimmunoassay of nicotine, cotinine, and gamma-(3-pyridyl)-gamma-oxo-N-methylbutyramide. , 1982 .

[11]  D. Phillips,et al.  Detection of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from coke oven workers: correlation with job categories. , 1992, Cancer research.

[12]  R. Harris,et al.  Tissue Typing Using a Routine One‐Step Lymphocyte Separation Procedure , 1970, British journal of haematology.

[13]  U. Meyer,et al.  Polymorphism of human acetyltransferases. , 1994, Environmental health perspectives.

[14]  C. Redmond,et al.  Occupationally Related Cancer Risk Among Coke Oven Workers: 30 Years of Follow-Up , 1995, Journal of occupational and environmental medicine.

[15]  D. Phillips,et al.  Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients. , 1994, Cancer research.

[16]  F. Perera,et al.  Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype. , 1997, Carcinogenesis.

[17]  L. V. van't Veer,et al.  32P-postlabelling of aromatic DNA adducts in white blood cells and alveolar macrophages of smokers: saturation at high exposures. , 1997, Mutation research.

[18]  F J van Schooten,et al.  Polycyclic aromatic hydrocarbon-DNA adducts in white blood cell DNA and 1-hydroxypyrene in the urine from aluminum workers: relation with job category and synergistic effect of smoking. , 1995, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[19]  J. Neese,et al.  Measurement of vitamin A and vitamin E in human serum by high-performance liquid chromatography. , 1982, Journal of chromatography.

[20]  G. Guanti,et al.  Cytogenetic studies in coke oven workers. , 1996, Toxicology letters.

[21]  H. Bartsch,et al.  Anti-benzo[a]pyrene diolepoxide--DNA adduct levels in peripheral mononuclear cells from coke oven workers and the enhancing effect of smoking. , 1995, Carcinogenesis.

[22]  P. Farmer.  Monitoring of human exposure to carcinogens through DNA and protein adduct determination. , 1995, Toxicology letters.

[23]  C. Vahrenholz,et al.  Risk estimation in coke-oven workers by determining some biomarkers of carcinogen exposure. , 1995, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[24]  Effect of glutathione S-transferase M1 polymorphisms on biomarkers of exposure and effects. , 1998 .

[25]  C. Redmond,et al.  Chromosomal aberrations and sister-chromatid exchanges in lymphocytes from coke oven workers. , 1988, Mutation research.

[26]  N K Spurr,et al.  Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. , 1993, Carcinogenesis.

[27]  C. Schell,et al.  32P-postlabeling analysis of DNA adducts in different populations. , 1995, Toxicology letters.

[28]  A. Haugen,et al.  Evaluation of biomarkers in plasma, blood, and urine samples from coke oven workers: significance of exposure to polycyclic aromatic hydrocarbons. , 1995, Occupational and environmental medicine.

[29]  F. Jongeneelen,et al.  Estimation of individual dermal and respiratory uptake of polycyclic aromatic hydrocarbons in 12 coke oven workers. , 1993, British journal of industrial medicine.

[30]  M. Kirsch‐Volders,et al.  Tumor markers in serum, polyamines and modified nucleosides in urine, and cytogenetic aberrations in lymphocytes of workers exposed to polycyclic aromatic hydrocarbons. , 1995, American journal of industrial medicine.

[31]  Juliane,et al.  DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers. , 1997, Occupational and environmental medicine.

[32]  G. Gabbani,et al.  GSTMI and NAT2 genotypes and urinary mutagens in coke oven workers , 1996 .

[33]  B. Mannervik,et al.  Molecular and catalytic properties of glutathione transferase mu from human liver: an enzyme efficiently conjugating epoxides. , 1983, Biochemistry.

[34]  R. Gupta,et al.  Enhanced sensitivity of 32P-postlabeling analysis of aromatic carcinogen:DNA adducts. , 1985, Cancer research.

[35]  M. Gardner,et al.  Confidence intervals rather than P values: estimation rather than hypothesis testing. , 1986, British medical journal.

[36]  J. Lewtas,et al.  DNA adducts and personal air monitoring of carcinogenic polycyclic aromatic hydrocarbons in an environmentally exposed population. , 1995, Carcinogenesis.

[37]  D. Grant,et al.  Human acetyltransferase polymorphisms. , 1997, Mutation research.

[38]  K. Hemminki,et al.  Relationship between hprt mutant frequency, aromatic DNA adducts and genotypes for GSTM1 and NAT2 in bus maintenance workers. , 1995, Carcinogenesis.

[39]  J. Lewtas,et al.  Czech-U.S. Epa Health Study: Assessment of Personal and Ambient Air Exposures to Pah and Organic Mutagens in the Teplice District of Northern Bohemia , 1994 .

[40]  A. Rannug,et al.  Assessment of genotoxic exposure in Swedish coke-oven work by different methods of biological monitoring. , 1991, Scandinavian journal of work, environment & health.

[41]  J. Lewtas,et al.  Air pollution exposure-DNA adduct dosimetry in humans and rodents: evidence for non-linearity at high doses. , 1997, Mutation research.

[42]  F P Perera,et al.  Contribution of genetic and nutritional factors to DNA damage in heavy smokers. , 1997, Carcinogenesis.