The influence of fluoranthene on the metabolism and DNA binding of benzo[ a]pyrene in vivo in mouse skin

Abstract

The effect of the cocarcinogen fluoranthene on the DNA binding and metabolism of [ 3 H]benzo[a] pyrene (B[a] P) in vivo in mouse skin has been investigated. In the presence of fluoranthene the level of B[ a]P-DNA binding was increased at each of the time intervals examined (4, 8, 24 and 48 h) with enhancements ranging from 76% at 4 h to 36% at 48 h. The ratio of anti-7,8,-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene ( anti-BPDE)-DNA adducts/ syn-BPDE-DNA adducts was also increased in the presence of fluoranthene. This increase was greatest at 8 h (44%) but by 48 h the ratio was identical in the presence and absence of fluoranthene. The observed increase in anti-BPDE-DNA adducts/ syn-BPDE-DNA adducts did not parallel increases in B[ a]P-DNA binding suggesting that alteration of the anti-BPDE/ syn-BPDE ratio is not a major contributing factor to the cocarcinogenic activity of fluoranthene. The influence of fluoranthene on the metabolism of B[ a]P in vivo in mouse skin was also investigated. Fluoranthene was found to have little or no effect on the formation of ethyl acetate extractable metabolites of B[ a]P in mouse skin. Specifically, there was no increase in the amount of B[ a]P-7,8-diol in the presence of fluoranthene. Fluoranthene also had little or no effect on the levels of β-glucuronide or sulfate conjugates of B[ a]P metabolites formed in vivo in mouse skin. These studies suggest that the effect of fluoranthene is being expressed at some point after B[ a]P has been activated to an ultimate carcinogen.