Metabolism of benzo[ a]pyrene and 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene in lung and liver of newborn mice

Abstract

Although the newborn mouse has been extensively used to test the tumorigenic activities of polynuclear aromatic hydrocarbons and their diol epoxide metabolites, no information is available on their metabolism in the newborn mouse in vivo. Therefore, we have investigated the metabolism and distribution of [ 3 H] benzo[a] pyrene ([ 3H]BaP) and (±)-7β,8α-[ 3 H] dihydroxy-9α,10α- epoxy-7,8,9,10- tetrahydrobenzo[a] pyrene ([ 3H]BPDE) in liver and lung of mice given i.p. injections of these compounds on their 1st, 8th and 15th days of life. In lung, identified metabolites of [ 3H]BaP included diols, quinones, and phenols. Their levels were higher on the 1st day compared to the 8th and 15th days of life. The pattern of organic extractable metabolites detected in mouse liver was different from that in lung, being dominated by unidentified polar metabolites, the levels of which increased with age. Levels of [ 3H]BPDE in liver and lung were measured by trapping with 2-mercaptoethanol. It was demonstrated that [ 3H]BPDE rapidly reaches the lung after i.p. injections. The half-lives of [ 3H]BPDE in lung and liver were similar to those observed in vitro. The results are discussed with respect to the known tumorigenic activities of BaP and BPDE in newborn mice and in mouse skin.