mezerein and Cell-Transformation--Viral

Cultured C3H/10T1/2 cells transfected with the plasmid pdBPV-1 were used as targets, and the frequency of transformed colonies as the endpoint to test the enhancing capacity of four promoters: 12-O-tetradecanoylphorbol-13-acetate (TPA), 4-O-methyl-tetradecanoylphorbol-13-acetate (4-O-methyl-TPA), mezerein and phorbol-12-retinoate-13-acetate (PRA). The frequency of the transfected C3H/10T1/2 cells to form transformed colonies was enhanced in the following order: mezerein greater than PRA greater than TPA greater than 4-O-methyl-TPA. The amount of promoters required to promote a tenfold increase in transformed cells was 0.24, 0.81, 30 and 100 ng/ml mezerein, PRA, TPA and 4-O-methyl-TPA, respectively. A significant promoting effect was obtained by a 3.5-day exposure to mezerein regardless of whether it was added at different time intervals after transfection with BPV-DNA. The examined promoters lacked genotoxic activity, as tested on Chinese hamster ovary cells, using chromatid aberrations and exchanges, frequency of macronuclei, unscheduled DNA synthesis (UDS) and inhibition of UDS as endpoints. The usefulness of BPV-1-induced transformation as a bioassay for detecting chemicals with promoting activities is discussed.

Topics: Animals; Bovine papillomavirus 1; Carcinogens; Cell Transformation, Viral; Chromosome Aberrations; Diterpenes; Mice; Mice, Inbred C3H; Micronucleus Tests; Papillomaviridae; Phorbol Esters; Sister Chromatid Exchange; Terpenes; Tetradecanoylphorbol Acetate