Genetic activity of diethylstilbestrol in Saccharomyces cerevisiae: enhancement of mutagenicity by oxidizing agents.
Diethylstilbestrol (DES), a synthetic estrogen, is known to cause cancer in humans and experimental animals. Although it has been established that DES can induce unscheduled DNA synthesis, sister-chromatid exchange, and cell transformation in various short-term tests, the efforts to demonstrate its mutagenic activity in bacterial and mammalian systems have largely failed. It has been shown that DES can covalently bind to DNA after being oxidized either chemically, in the presence of iodine and hydrogen peroxide, or metabolically, by mammalian cells in tissue culture and also in the presence of rat-liver microsomes. We studied genetic activity of DES in growing cultures of the strains XV185-14C and D5 of S. cerevisiae in the presence and absence of oxidizing agents, namely, iodine and hydrogen peroxide. We demonstrated that DES alone exhibits a weak mutagenic response in the strain XV185-14C. On the other hand, the treatment of cells with DES in the presence of iodine or hydrogen peroxide plus ferrous sulfate induced a large increase in the frequency of induced mutations in strain XV185-14C and mitotic recombination and gene conversion in strain D5. This enhancement in the genetic activity of DES in our test assays in the presence of chemical oxidative systems indicates that DES undergoes oxidation to produce a genetically active metabolite.
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004357:Drug Synergism; D005785:Gene Conversion; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007455:Iodine / Q000494:pharmacology*; D008433:Mathematics; D009152:Mutagenicity Tests; D009153:Mutagens; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism
D009153:Mutagens; D004054:Diethylstilbestrol; D003577:Cytochrome P-450 Enzyme System; D007455:Iodine; D006861:Hydrogen Peroxide