The chemistry and biology of 7H-dibenzo(c,g)carbazole: synthesis and characterization of selected derivatives, metabolism in rat liver preparations and mutagenesis mediated by cultured rat hepatocytes.
Strong-DB; Christian-RT; Jayasimhulu-K; Wilson-RM; Warshawsky-D
Carcinogenesis 1989 Mar; 10(3):419-427
The synthesis and complete characterization of stable standards needed in support of previously published work and the results of current investigations into the metabolism and activation of 7H- dibenzo(c,g)carbazole (194592) (DBC) were presented. The study indicated that phenols were the predominant metabolites of DBC, which suggests that either the intermediates undergo intramolecular rearrangement more readily than polycyclic aromatic hydrocarbons (PAH) or related N-heterocyclic polynuclear aromatic compounds (NPA), or that oxidation was exclusively by direct hydroxylation. Phenols were formed either by intramolecular rearrangement of epoxides or through direct hydroxylation of a specific position in the molecule. Such reactions would be consistent with the high reactivity of DBC intermediates based on its observed carcinogenic activity. The rate of metabolism of DBC by rat liver cells at high substrate concentrations was greater than that for benzo(a)pyrene (BaP) and at lower concentrations DBC was more efficient at producing mutations than BaP. Mutagenic activity of specific phenols that were identified as metabolites was associated only with compounds related to the nitrogen by induction. Derivatives not identified as metabolites but still associated with the nitrogen by induction were also mutagenic, supporting the hypothesis that the nitrogen is involved in the activation of the compound.
NIOSH-Publication; NIOSH-Grant; Cancer; Mutagenesis; Metabolic-study; Laboratory-animals; Liver-cells; Hepatotoxicity; Carbazoles; Polynuclear-aromatic-hydrocarbons; Carcinogens
Environmental Health University of Cincinnati 3223 Eden Avenue Cincinnati, Ohio 45267
University of Cincinnati, Cincinnati, Ohio