Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis

Stephen W. Ashurst, Thomas J. Slaga, Gerald M. Cohen, Di Giovanni John

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

The tumorigenicity of benzo(a)pyrene [B(a)P] applied topically as a skin tumor initiator in Senear 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/deoxyribonu-cleoside adduct formed cochromatographed with marker adducts of N2-{10S-[7R,8S,9R-trihydroxy-7,8,9, 10-tetrahydro-benzo(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.

Original languageEnglish (US)
Pages (from-to)1024-1029
Number of pages6
JournalCancer Research
Volume43
Issue number3
StatePublished - Mar 1983

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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