Reduction of Tumorigenicity and of Dihydrodiol Formation by Fluorine Substitution in the Angular Rings of Dibenzo(a, i)pyrene

Stephen S. Hecht, Edmond J. LaVoie, Victoria Bedenko, Linda Pingaro, Shoichi Katayama, D. Dietrich

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The tumor-initiating activities on mouse skin and in vitro metabolism of dibenzo(a, i)pyrene, 2-fluorodibenzo(a, i)pyrene, 3-fluorodibenzo(a, i)pyrene, and 2,10-difluorodibenzo(a, i)py-rene were compared. After an initiating dose of 500 μg, followed by promotion with tetradecanoylphorbol acetate, di-benzo(a, i)pyrene induced skin tumors in 85% of the mice and caused 5.8 skin tumors/mouse. The corresponding tumorigenic activities for the fluorinated compounds were: 2-fluoro-dibenzo(a, i)pyrene (85%; 1.7 tumors/mouse); 3-fluorodi-benzo(a, i)pyrene (80%; 3.1 tumors/mouse); and 2,10-difluo-rodibenzo(a, i)pyrene (10%; 0.1 tumors/mouse). After an initiating dose of 100 μg, only dibenzo(a, i)pyrene showed significant tumor-initiating activity. 3,4-Dihydro-3,4-dihydroxydi-benzo(a,/)pyrene was identified as a metabolite of dibenzo(a, i)pyrene formed by the 9000 x g supernatant from the livers of Aroclor 1254-pretreated rats. Another dihydrodiol was tentatively identified as 1,2-dihydro-1,2-dihydroxydiben-zo(a, i)pyrene. The formation of these angular ring dihydrodiols was inhibited in the metabolism of 2-fluorodiben-zo(a, Opyrene and 3-fluorodibenzo(a, i)pyrene. Angular ring dihydrodiols were not detected in the metabolism of 2,10-di-fluorodibenzo(a, i)pyrene. These results suggest that an angular ring dihydrodiol, 3,4-dihydro-3,4-dihydroxydi-benzo(a, i)pyrene, which can form a bay-region dihydrodiol epoxide, may be a proximate carcinogen of dibenzo(a, i)pyrene.

Original languageEnglish (US)
Pages (from-to)4341-4345
Number of pages5
JournalCancer Research
Volume41
StatePublished - Jul 1 1981

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