Nonspecific inhibition of DNA repair by promoting and nonpromoting phorbol esters.
The effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and its nonpromoting structural analogue, 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate (Me-TPA), on N-acetoxy-2-acetylaminofluorene-elicited DNA repair and replicative DNA synthesis was measured in normal human fibroblasts. Both esters inhibited DNA repair synthesis, and Me-TPA was nearly as effective as TPA. In addition, TPA inhibited replicative DNA synthesis. These findings showed that inhibition of DNA repair synthesis may not be a major factor in the mechanisms of action of tumor promoters.
D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D010704:Phorbols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology*
D010704:Phorbols; D000099:Acetoxyacetylaminofluorene; D013755:Tetradecanoylphorbol Acetate