chapter  8
37 Pages

Comparative Carcinogenicity, Metabolism, Mutagenicity, and DNA Binding of 7H-Dibenzo[c,g]carhazole and Dibenz[a,j]acridine

WithDavid Warshawsky, Glenn Talaska, Weiling Xue, Joanne Schneider

This chapter addresses what is known about 7H-dibenzo (c,g)carbazole (DBC) and dibenz (a,j) acridine (DBA), and compares and contrasts the results obtained for their carcinogenicity, metabolism, mutagenicity, and DNA binding. Short-term DBC-DNA binding studies using radiolabeled DBC indicated that there was significant covalent reaction in vivo. DBC has both local and systemic effects in the mouse; it is a potent skin and liver carcinogen following topical application and a lung carcinogen following Intraperitoneal application. DBA is a moderate mouse skin carcinogen following topical application and a lung carcinogen following subcutaneous injection. The biological differences for DBC and DBA are reflected in target organ-specific proximate and mutagenic metabolites and DNA adduct patterns. The formation of reactive metabolites, specifically DNA binding species, appears to be a critical step in the carcinogenicity of many chemical carcinogens. Experimental evidence indicates that carcinogen-DNA adducts are associated with chromosome breakage and point mutations.