COMPARATIVE CARCINOGENICITY, METABOLISM, MUTAGENICITY, AND DNA-BINDING OF 7H-DIBENZO[C,G]CARBAZOLE AND DIBENZ[A,J]ACRIDINE

Complex mixtures that are produced from the combustion of organic mate rials have been associated with increased cancer mortality. These mixt ures contain homocyclic and heterocyclic polycyclic aromatic hydrocarb ons (PAHs), many of which are known carcinogens. In particular, N-hete rocyclic aromatic compounds (NHA) are present in these mixtures. Studi es to determine the metabolic activation of these compounds have been undertaken. The purpose of this review is to compare and contrast the metabolic activation and biological effects of two NHA, 7H-dibenzo[c,g ]carbazole(DBC) and dibenz[a,j]acridine (DBA), in order to better asse ss the contribution of NHA to the carcinogenic potency of complex mixt ures and to develop biomarkers of the carcinogenic process. DBC has bo th local and systemic effects in the mouse; it is a potent skin and li ver carcinogen following topical application and a lung carcinogen fol lowing i.p. application. On the other hand, DBA is a moderate mouse sk in carcinogen following topical application and a lung carcinogen foll owing subcutaneous injection. The biological differences for DBC and D BA are reflected in target organ-specific proximate and mutagenic meta bolites and DNA adduct patterns.