FAILURE OF THE PHORBOL ESTER 12-O-TETRADECANOYLPHORBOL-13-ACETATE TO ENHANCE SISTER CHROMATID EXCHANGE, MITOTIC SEGREGATION, OR EXPRESSION OF MUTATIONS IN CHINESE-HAMSTER CELLS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (9) , 3245-3251
Abstract
The potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was tested for its ability to induce sister chromatid exchange, to increase the rate of transition at the adenine phosphoribosyltransferase (aprt) locus from the presumptive heterozygous state (+/-) to the homozygous state (-/- or -), and to enhance the frequency of mutations expressed after UV radiation mutagenesis. No significant effect of TPA was found. Sister chromatid exchange frequencies in Chinese hamster ovary and [lung] V79 cells remained unchanged by TPA treatment under various conditions, a result inconsistent with the hypothesis that an important effect of TPA might be to increase the rate of chromosomal mitotic recombination (and hence segregation of recessive mutations) in a manner akin to increased chromatid recombination. No evidence was found for mitotic recombination affecting the aprt locus in Chinese hamster ovary cells for which the rate of change to a high level of resistance to azaadenine was measured. The rate of 8.6 .times. 10-7 mutation (and/or segregations) per cell generation assessed by fluctuation analysis was not increased by the continuous presence of TPA, 4 .mu.g/ml, in the medium. Mutant frequencies in Chinese hamster ovary cells after UV mutagenesis were measured for the markers ouabain resistance, thioguanine resistance and azaadenine resistance, with and without pretreatment with TPA before mutant selection. No convincing enhancement in mutation expression was observed. Promotion by TPA apparently does not proceed by a mechanism involving genetic recombination or the altered expression of newly mutated alleles.