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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Oct;82(19):6672–6676. doi: 10.1073/pnas.82.19.6672

Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers.

C C Harris, K Vahakangas, M J Newman, G E Trivers, A Shamsuddin, N Sinopoli, D L Mann, W E Wright
PMCID: PMC391272  PMID: 2413443

Abstract

Coke oven workers are exposed to high levels of carcinogenic polycyclic aromatic hydrocarbons, including benzo[a]pyrene (B[a]P), and are at increased risk of lung cancer. Since B[a]P is enzymatically activated to 7 beta,8 alpha-dihydroxy(9 alpha, 10 alpha)epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE) that forms adducts with DNA, the presence of these adducts was measured in DNA from peripheral blood lymphocytes by synchronous fluorescence spectrophotometry and enzyme radioimmunoassay. Approximately two-thirds of the workers had detectable levels of B[a]PDE-DNA adducts. Antibodies to the DNA adducts were also found in the serum of 27% of the workers. B[a]PDE-DNA adducts were not detectable in lymphocytes and antibodies to the adducts were not detected in sera from a control group of nonsmoking laboratory workers. DNA adducts and/or antibodies to the adducts indicate exposure to B[a]P and its metabolic activation to the carcinogenic metabolite that covalently binds to and damages DNA. Detection of adducts and antibodies to them may also be useful as internal dosimeters of the pathobiological effective doses of chemical carcinogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashurst S. W., Cohen G. M., Nesnow S., DiGiovanni J., Slaga T. J. Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis. Cancer Res. 1983 Mar;43(3):1024–1029. [PubMed] [Google Scholar]
  2. Dubroff L. M., Reid R. J., Jr Hydralazine-pyrimidine interactions may explain hydralazine-induced lupus erythematosus. Science. 1980 Apr 25;208(4442):404–406. doi: 10.1126/science.7367866. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Harris C. C., Yolken R. H., Krokan H., Hsu I. C. Ultrasensitive enzymatic radioimmunoassay: application to detection of cholera toxin and rotavirus. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5336–5339. doi: 10.1073/pnas.76.10.5336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsu I. C., Poirier M. C., Yuspa S. H., Grunberger D., Weinstein I. B., Yolken R. H., Harris C. C. Measurement of benzo(a)pyrene-DNA adducts by enzyme immunoassays and radioimmunoassay. Cancer Res. 1981 Mar;41(3):1091–1095. [PubMed] [Google Scholar]
  7. 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]
  8. Kulkarni M. S., Anderson M. W. Persistence of benzo(a)pyrene metabolite:DNA adducts in lung and liver of mice. Cancer Res. 1984 Jan;44(1):97–101. [PubMed] [Google Scholar]
  9. Müller R., Rajewsky M. F. Antibodies specific for DNA components structurally modified by chemical carcinogens. J Cancer Res Clin Oncol. 1981;102(2):99–113. doi: 10.1007/BF00410662. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Poirier M. C. Antibodies to carcinogen-DNA adducts. J Natl Cancer Inst. 1981 Sep;67(3):515–519. [PubMed] [Google Scholar]
  12. Rahn R. O., Chang S. S., Holland J. M., Shugart L. R. A fluorometric-HPLC assay for quantitating the binding of benzo[a]pyrene metabolites to DNA. Biochem Biophys Res Commun. 1982 Nov 16;109(1):262–268. doi: 10.1016/0006-291x(82)91594-7. [DOI] [PubMed] [Google Scholar]
  13. Reddy M. V., Gupta R. C., Randerath E., Randerath K. 32P-postlabeling test for covalent DNA binding of chemicals in vivo: application to a variety of aromatic carcinogens and methylating agents. Carcinogenesis. 1984 Feb;5(2):231–243. doi: 10.1093/carcin/5.2.231. [DOI] [PubMed] [Google Scholar]
  14. Redmond C. K., Ciocco A., Lloyd J. W., Rush H. W. Long-term mortality study of steelworkers. VI. Mortality from malignant neoplasms among coke oven workers. J Occup Med. 1972 Aug;14(8):621–629. [PubMed] [Google Scholar]
  15. Reidenberg M. M., Drayer D. E. Aromatic amines and hydrazines drug acetylation, and lupus erythematodes. Hum Genet Suppl. 1978;(1):57–63. doi: 10.1007/978-3-642-67179-1_8. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Uetrecht J. P., Freeman R. W., Woosley R. L. The implications of procainamide metabolism to its induction of lupus. Arthritis Rheum. 1981 Aug;24(8):994–1003. doi: 10.1002/art.1780240803. [DOI] [PubMed] [Google Scholar]
  18. Warnke R., Levy R. Detection of T and B cell antigens hybridoma monoclonal antibodies: a biotin-avidin-horseradish peroxidase method. J Histochem Cytochem. 1980 Aug;28(8):771–776. doi: 10.1177/28.8.7003003. [DOI] [PubMed] [Google Scholar]

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