A
complex mixture of
polycyclic aromatic hydrocarbons (PAH) extracted from
coal tar, standard reference material (
SRM) 1597, has been shown to initiate
tumor formation in mouse initiation-promotion assays in our laboratory [(2001)
Carcinogenesis 22 (7), 1077-1086]. To determine the effects of
SRM 1597 on PAH activation in human cells, we investigated the
PAH-DNA adduct formation in the
human mammary carcinoma-derived cell line MCF-7. We examined the effects of
SRM 1597 on the metabolic activation to
DNA binding derivatives of two carcinogenic PAHs, the bay region containing
benzo[a]pyrene (B[a]P) and the more carcinogenic fjord region containing
dibenzo[a,l]pyrene (DB[a,l]P).
PAH-DNA adduct analysis by 33P-postlabeling and reversed phase high-performance liquid chromatography revealed a significant decrease in the levels of both B[a]P and DB[a,l]P
DNA adduct formation on cotreatment with
SRM 1597 in comparison to cells exposed to B[a]P or DB[a,l]P alone. However, the inhibition of
PAH-DNA adduct formation only occurred within the first 48 h of exposure in cells cotreated with
SRM 1597 and B[a]P. In contrast,
SRM 1597 significantly inhibited the level of DB[a,l]P
DNA adducts throughout the 120 h of exposure. Induction of human
cytochrome P450 (
P450) enzymes 1A1 and P4501B1 on treatment with
SRM 1597 was observed by immunoblots. These results suggest that the important factors in determining the carcinogenic activity of PAH within a
complex mixture would depend on the ability of other components of the mixture to promote or inhibit the activation of carcinogenic PAH by the induction of
P450 enzymes followed by the formation of
DNA adducts.