FURTHER-STUDIES ON THE COMUTAGENIC ACTIVITY OF CIGARETTE-SMOKE CONDENSATE

The comutagenic effect exerted by cigarette smoke condensate (CSC) was investigated. In vitro experiments with Salmonella typhimurium strains TA98 and TA98/1, 8DNP6 indicated that CSC specifically enhances the mutagenicity of polyaromatic amines such as 2-aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-aminoanthracene. The pattern of comutagenicity of CSC was shown to differ from that of norharman, a tobacco-related known comutagenic substance. Both black and blond tobacco CSCs proved to interact synergistically with 2-aminoanthracene mutagenicity. Chemical fractionation of CSC indicates the occurrence of comutagenic substance(s) in both neutral and basic components. Further in vitro experiments with 2-acetylaminofluorene metabolites and derivatives suggest that the comutagenic effect of CSC could involve later step(s) in the metabolic activation of fluorenylamines, i.e., the conversion of hydroxylamines into ultimate reactive species. The possible occurrence of a synergistic interaction of CSC with chemical mutagens in vivo was evaluated. Administration of 2-aminoanthracene/CSC mixtures, previously shown to be comutagenic in vitro, failed to demonstrate a synergistic effect in SCE induction in bone marrow cells of mice. This apparent discrepancy may rely on divergences in the activation pathways of polycyclic amines in vitro and in vivo.