The skin
tumor-initiating activities of 7-, 8-, 9-, and 10-fluorobenzo(a)pyrenes have been compared to that of
benzo(a)pyrene in female Sencar mice after 16 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Single initiating doses of 200 or 400 nmol of each
hydrocarbon were tested, and the mice were treated twice weekly with 3.2 nmol of the promoter. Under these conditions,
benzo(a)pyrene caused an average of 2.9 and 5.7
papillomas/mouse, respectively, whereas none of the four
fluorinated hydrocarbons had significant
tumor-initiating activity. Examination of the hepatic metabolism of 7- and
8-fluorobenzo(a)pyrene revealed that a 7,8-dihydrodiol was not detected as a metabolite; thus, the bay-region diol-
epoxide pathway known to be responsible for the tumorigenic activity of
benzo(a)pyrene is blocked. Although 7,8-dihydrodiols are formed from 9- and
10-fluorobenzo(a)pyrene, these dihydrodiols with
fluorine substituted on the 9,10-double bond may not be converted to diol-
epoxides by the
cytochrome P-450 system, or such fluorinated 7,8-diol-9,10-epoxides may not be tumorigenic.