Investigation of the effects of the phorbol ester TPA on carcinogen-induced forward mutagenesis to 6-thioguanine-resistance in V79 Chinese hamster cells.

Abstract

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) was tested for its effect on N'-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced forward mutagenesis to 6-thioguanine resistance (6TGR) in V79 Chinese hamster cells. Using a replating assay, no effect of TPA on the recovery of 6TGR mutants was observed. Previous reports of TPA enhancement of carcinogen-induced forward mutagenesis using the in situ mutagenesis assay, can be explained in terms of the influence of metabolic co-operation on mutant recovery. TPA is known to eliminate metabolic co-operation, an artefact of the in situ mutagenesis assay system, thus contributing to the enhancement of mutant recovery in TPA treated cultures. This investigation aims to demonstrate that TPA has no influence on mutagenesis per se, positive or negative enhancement of forward mutagenesis being solely a reflection of the mutagenesis assay employed.