Inhibitory effects of the phorbolester TPA and cigarette smoke condensate on the mutagenicity of benzo[a]pyrene in a co-cultivation system.
The transport of reactive intermediates was studied in a co-cultivation system of primary chick embryo hepatocytes and V79 Chinese hamster cells. Two test systems with different genetic endpoints--sister-chromatid exchange (SCE) and gene mutation at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus--were used. Benzo[a]pyrene (B[a]P) was positive in both test systems. When the V79 cells were co-cultivated with the hepatocytes at a distance of 1 mm, only a slight increase in the number of SCEs was observed after exposure to benzo[a]pyrene. When the two cell types were in direct contact, addition of the phorbolester TPA or cigarette smoke condensate inhibited the mutagenic effects of B[a]P in both assays by 50%. No influence of TPA on the number of SCEs induced by B[a]P was observed in a preincubation assay using Aroclor-1254-induced rat liver homogenate. The results indicate that metabolic co-operation may play a role in the transport of reactive intermediates in this co-cultivation system. The mutagenic potential of compounds may be underestimated in systems using intact cells for metabolic activation if the compounds or their metabolites are capable of inhibiting metabolic co-operation.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D002450:Cell Communication / Q000187:drug effects; D002642:Chick Embryo; D006224:Cricetinae; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007365:Intercellular Junctions / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D009154:Mutation / Q000187:drug effects; D010704:Phorbols / Q000494:pharmacology*; D010947:Plants, Toxic; D012854:Sister Chromatid Exchange / Q000187:drug effects; D012906:Smoke; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014026:Nicotiana
D010704:Phorbols; D012906:Smoke; D001564:Benzo(a)pyrene; D007041:Hypoxanthine Phosphoribosyltransferase; D013755:Tetradecanoylphorbol Acetate