These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Enhancement of recovery of chemical carcinogen-induced ouabain-resistant mutants in Chinese hamster cells by the tumor-promoting agent, 12-o-tetradecanoyl-phorbol-13-acetate.
    Author: Lankas GR, Baxter CS, Christian RT.
    Journal: Mutat Res; 1980 Dec; 73(2):319-29. PubMed ID: 7464841.
    Abstract:
    The effects of a tumor-promoting agent on the frequency of mutation to ouabain resistance and survival of Chinese hamster cells treated with a chemical carcinogen have been investigated. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) significantly enhanced the mutation frequency induced by the carcinogen, methylazoxymethanol acetate (MAM), without having similar effects on cytotoxicity, at concentrations of 2 micrograms/ml or less. The observed degree of enhancement of mutagenesis increased with promoter concentration up to the point where the latter exhibited frank toxicity. Exposure of the cells to the promoter for a period of 2 or 6 h was found ineffective, but subsequently a significant enhancement was found after a 27-h exposure time. The maximum effect occurred after a 5-day exposure, with a increase in the mutation frequency of 250%. Treatment of cells with TPA alone resulted in no enhancement of spontaneous mutation rates, nor did treatment of cells prior to addition of carcinogen-induced mutagenesis. In contrast, TPA was found to be effective when applied as late as 6 weeks following carcinogen treatment. These results are consistent with the hypothesis that TPA owes its promoting activity toward chemically-induced mutagenesis and carcinogenesis to its ability to enhance expression of latent somatic genetic modifications by epigenetic mechanisms. They do not support mechanisms involving TPA-induced inhibition of DNA-repair replication, or mutagenic activity of TPA per se. The notably similar qualitative response to TPA of several parameters in mouse-skin tumorigenesis and Chinese hamster cell mutagenesis suggest that the mechanism of action of the promoter is similar in the 2 diverse biological systems.
    [Abstract] [Full Text] [Related] [New Search]