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

S. W. Ashurst, Thomas J Slaga, S. Nesnow, J. DiGiovanni, T. J. Slaga

Research output: Contribution to journalArticle

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Abstract

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 N 2-{10S-[7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl}/deoxyg uanosine 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 - 1983
Externally publishedYes

Fingerprint

Deoxyribonucleosides
Benzo(a)pyrene
Epidermis
Neoplasms
DNA
Hydrocarbons
Skin
Papilloma
Carcinogens
Radioactivity
benzo(a)pyrene-DNA adduct

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ashurst, S. W., Slaga, T. J., Nesnow, S., DiGiovanni, J., & Slaga, T. J. (1983). Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis. Cancer Research, 43(3), 1024-1029.

Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis. / Ashurst, S. W.; Slaga, Thomas J; Nesnow, S.; DiGiovanni, J.; Slaga, T. J.

In: Cancer Research, Vol. 43, No. 3, 1983, p. 1024-1029.

Research output: Contribution to journalArticle

Ashurst, SW, Slaga, TJ, Nesnow, S, DiGiovanni, J & Slaga, TJ 1983, 'Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis', Cancer Research, vol. 43, no. 3, pp. 1024-1029.
Ashurst, S. W. ; Slaga, Thomas J ; Nesnow, S. ; DiGiovanni, J. ; Slaga, T. J. / Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis. In: Cancer Research. 1983 ; Vol. 43, No. 3. pp. 1024-1029.
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