Abstract
The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz[a]anthracene and benzo[a]pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactions between the benzo[a]pyrene and the chrysene diol-epoxide adducts were present. Similar cross-reactivity between the benz[a]anthracene and the chrysene adducts was observed. Sera containing antibodies that were apparently specific for each of the three PAH-DNA adducts were also identified. The presence of antibodies to PAH-DNA adducts indicates both past exposure to these carcinogenic PAH and their metabolic activation to the DNA damaging metabolites. These antibodies may prove to be useful in both retrospective and prospective epidemiological studies of various diseases associated with PAH exposure.
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Selected References
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- Ayesh R., Idle J. R., Ritchie J. C., Crothers M. J., Hetzel M. R. Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature. 1984 Nov 8;312(5990):169–170. doi: 10.1038/312169a0. [DOI] [PubMed] [Google Scholar]
- Conney A. H. Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture. Cancer Res. 1982 Dec;42(12):4875–4917. [PubMed] [Google Scholar]
- Evans D. A., Harmer D., Downham D. Y., Whibley E. J., Idle J. R., Ritchie J., Smith R. L. The genetic control of sparteine and debrisoquine metabolism in man with new methods of analysing bimodal distributions. J Med Genet. 1983 Oct;20(5):321–329. doi: 10.1136/jmg.20.5.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Evans D. A., Mahgoub A., Sloan T. P., Idle J. R., Smith R. L. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet. 1980 Apr;17(2):102–105. doi: 10.1136/jmg.17.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gelboin H. V. Benzo[alpha]pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiol Rev. 1980 Oct;60(4):1107–1166. doi: 10.1152/physrev.1980.60.4.1107. [DOI] [PubMed] [Google Scholar]
- Giles R. C., Capra J. D. Structure, function, and genetics of human class II molecules. Adv Immunol. 1985;37:1–71. doi: 10.1016/s0065-2776(08)60337-5. [DOI] [PubMed] [Google Scholar]
- Grover P. L., Hewer A., Pal K., Sims P. The involvement of a diol-epoxide in the metabolic activation of benzo(a)pyrene in human bronchial mucosa and in mouse skin. Int J Cancer. 1976 Jul 15;18(1):1–6. doi: 10.1002/ijc.2910180102. [DOI] [PubMed] [Google Scholar]
- Gupta R. C. Enhanced sensitivity of 32P-postlabeling analysis of aromatic carcinogen:DNA adducts. Cancer Res. 1985 Nov;45(11 Pt 2):5656–5662. [PubMed] [Google Scholar]
- Harris C. C., Autrup H., Connor R., Barrett L. A., McDowell E. M., Trump B. F. Interindividual variation in binding of benzo[a]pyrene to DNA in cultured human bronchi. Science. 1976 Dec 3;194(4269):1067–1069. doi: 10.1126/science.982061. [DOI] [PubMed] [Google Scholar]
- Harris C. C., Trump B. F., Grafstrom R., Autrup H. Differences in metabolism of chemical carcinogens in cultured human epithelial tissues and cells. J Cell Biochem. 1982;18(3):285–294. doi: 10.1002/jcb.1982.240180304. [DOI] [PubMed] [Google Scholar]
- Harris C. C., Vahakangas K., Newman M. J., Trivers G. E., Shamsuddin A., Sinopoli N., Mann D. L., Wright W. E. Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6672–6676. doi: 10.1073/pnas.82.19.6672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haverkorn M. J., Hofman B., Masurel N., Rood J. J. HL-A linked genetic control of immune response in man. Transplant Rev. 1975;22:120–124. doi: 10.1111/j.1600-065x.1975.tb01554.x. [DOI] [PubMed] [Google Scholar]
- Jeffrey A. M., Weinstein I. B., Jennette K. W., Grzeskowiak K., Nakanishi K., Harvey R. G., Autrup H., Harris C. Structures of benzo(a)pyrene--nucleic acid adducts formed in human and bovine bronchial explants. Nature. 1977 Sep 22;269(5626):348–350. doi: 10.1038/269348a0. [DOI] [PubMed] [Google Scholar]
- Lee M. L., Novotny M., Bartle K. D. Gas chromatography/mass spectrometric and nuclear magnetic resonance spectrometric studies of carcinogenic polynuclear aromatic hydrocarbons in tobacco and marijuana smoke condensates. Anal Chem. 1976 Feb;48(2):405–416. doi: 10.1021/ac60366a048. [DOI] [PubMed] [Google Scholar]
- Mann D. L., Mendell N., Kahn C. R., Johnson A. H., Rosenthal A. In vitro lymphocyte proliferation response to therapeutic insulin components. Evidence for genetic control by the human major histocompatibility complex. J Clin Invest. 1983 Sep;72(3):1130–1138. doi: 10.1172/JCI111038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Masuda Y., Kuratsune M. Comparison of the yield of polycyclic aromatic hydrocarbons in smoke from Japanese tobacco. Nihon Eiseigaku Zasshi. 1972 Aug;27(3):339–341. doi: 10.1265/jjh.27.339. [DOI] [PubMed] [Google Scholar]
- Perera F. P., Poirier M. C., Yuspa S. H., Nakayama J., Jaretzki A., Curnen M. M., Knowles D. M., Weinstein I. B. A pilot project in molecular cancer epidemiology: determination of benzo[a]pyrene--DNA adducts in animal and human tissues by immunoassays. Carcinogenesis. 1982;3(12):1405–1410. doi: 10.1093/carcin/3.12.1405. [DOI] [PubMed] [Google Scholar]
- Pulkrabek P., Leffler S., Weinstein I. B., Grunberger D. Conformation of DNA modified with a dihydrodiol epoxide derivative of benzo[a]pyrene. Biochemistry. 1977 Jul 12;16(14):3127–3132. doi: 10.1021/bi00633a014. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H. Immune response (Ir) genes of the murine major histocompatibility complex. Adv Immunol. 1986;38:31–201. doi: 10.1016/s0065-2776(08)60006-1. [DOI] [PubMed] [Google Scholar]
- Shamsuddin A. K., Sinopoli N. T., Hemminki K., Boesch R. R., Harris C. C. Detection of benzo(a)pyrene:DNA adducts in human white blood cells. Cancer Res. 1985 Jan;45(1):66–68. [PubMed] [Google Scholar]
- Shugart L. Quantitating exposure to chemical carcinogens: in vivo alkylation of hemoglobin by benzo[a]pyrene. Toxicology. 1985 Mar 15;34(3):211–220. doi: 10.1016/0300-483x(85)90172-6. [DOI] [PubMed] [Google Scholar]
- Sims P., Grover P. L., Swaisland A., Pal K., Hewer A. Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide. Nature. 1974 Nov 22;252(5481):326–328. doi: 10.1038/252326a0. [DOI] [PubMed] [Google Scholar]
