DNA Adducts and Carcinogenicity of Nitro-polycyclic Aromatic Hydrocarbons

Abstract

We have studied in vitro metabolism, DNA adduct formation, mutagenicity, and tumorigenicity of a series of nitro−polycyclic aromatic hydrocarbons. The emphasis has been focused on the isomeric nitrobenzo−[a]pyrenes and related compounds. We have previously shown that in vitro there are multiple pathways for the mutagenic activation of 1− and 3−nitro−BaP. In this paper we report that DNA adducts formed from nitroreduction of 1− and 3−nitro−BaP involve a long range migration. DNA adducts from the ultimate metabolites, the bay−region trans−7,8−diol−anti−9, 10−epoxides of 1− and 3−nitro−BaPs have also been obtained. We have also found that a nitro−PAH with its nitro functional group perpendicular to the aromatic moiety exhibits less tumorigenicity than the parent PAH.

Key Words:

• Nitro−polycyclic aromatic hydrocarbons
• nitrobenzo[a]pyrene
• in vitro metabolism
• DNA adduct
• tumorigenicity
• diol−epoxide