This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ashurst, S. W. Articles by Slaga, T. J. Search for Related Content PubMed PubMed Citation Articles by Ashurst, S. W. Articles by Slaga, T. J.

Formation of Benzo(a)pyrene/DNA Adducts and Their Relationship to Tumor Initiation in Mouse Epidermis¹

Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 [S. W. A., T. J. S.], Toxicology Unit, Department of Pharmacology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WCI IAX, England [G. M. C.], Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina [S. N.], and The Wistar Institute, Philadelphia, Pennsylvania 19104 [J. D.]

The tumorigenicity of benzo(a)pyrene [B(a)P] applied topically as a skin tumor initiator in Sencar mice and the formation of epidermal B(a)P/deoxyribonucleoside adducts were compared over a similar range of doses (50 to 1600 nmol). The tumor-initiating activity of B(a)P, its covalent binding to mouse epidermal DNA, and the formation of the major hydrocarbon/deoxyribonucleoside adduct showed approximately parallel dose-response curves. The major hydrocarbon/deoxyribonucleoside adduct formed cochromatographed with marker adducts of N²-{10S-[7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl}/deoxyguanosine while other minor adducts also were observed. The disappearance of DNA-bound products in the epidermis was followed for 21 days after an initiating dose of B(a)P (100 nmol) was applied topically to the mice. The half-lives of the B(a)P/deoxyribonucleoside adducts and the total radioactivity bound to the DNA were 4.5 and 5.5 days, respectively. However, in spite of the loss of measurable DNA-bound material, the tumor yield was unchanged regardless of whether promotion was begun 7 or 21 days after initiation. The results suggest a possible causal relationship between B(a)P/deoxyribonucleoside adduct formation and papilloma formation in mouse skin.

¹ Research was supported by NIH Grants CA-21778, CA-10815, CA-09104, and CA-20076, and by the United States Department of Energy Contract No. 79D-X0526 under the Interagency Agreement, United States Department of Energy No. 40-728-78.

² To whom requests for reprints should be addressed.

Received 7/19/82. Accepted 12/ 1/82.

This article has been cited by other articles:

				R. L. Divi, F. A. Beland, P. P. Fu, L. S. Von Tungeln, B. Schoket, J. E. Camara, M. Ghei, N. Rothman, R. Sinha, and M. C. Poirier Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring Carcinogenesis, December 1, 2002; 23(12): 2043 - 2049. [Abstract] [Full Text] [PDF]

				P. G. Shields Tobacco Smoking, Harm Reduction, and Biomarkers J Natl Cancer Inst, October 2, 2002; 94(19): 1435 - 1444. [Abstract] [Full Text] [PDF]

				S. Nesnow, C. Davis, W. T. Padgett, L. Adams, M. Yacopucci, and L. C. King 8,9-Dihydroxy-8,9-dihydrodibenzo[a,l]pyrene is a potent morphological cell-transforming agent in C3H10T1/2Cl8 mouse embryo fibroblasts in the absence of detectable stable covalent DNA adducts Carcinogenesis, June 1, 2000; 21(6): 1253 - 1257. [Abstract] [Full Text] [PDF]