Mechanisms of cisplatin (cis-diamminodichloroplatinum II)-induced cytotoxicity and genotoxicity in yeast

Mutat Res. 1984 Jun;127(1):23-30. doi: 10.1016/0027-5107(84)90136-2.

Abstract

The antitumor drug, cisplatin (cis- diamminodichloroplatinum II), dissolved in both water and phosphate-buffered saline, was studied for its genotoxic and cytotoxic effects in the yeast, Saccharomyces cerevisiae. The results showed that the drug was both recombinagenic and mutagenic in the wild-type diploid strain D7. It was observed that both cytotoxicity and genotoxicity were greatly reduced when cisplatin was dissolved in phosphate-buffered saline compared to the aqueous solution. Cell survival analyses showed that the diploid strain (D7 rad 3), deficient in excision of UV-induced pyrimidine dimers or similar adducts, was hypersensitive to cisplatin. Another diploid strain (rad 52/rad 52), blocked in the repair of DNA double-strand breaks and recombination was also hypersensitive to the drug. Mitotic gene conversion was not observed in the rad 52/rad 52 diploid after the drug treatments, while it was reduced in the excision -deficient strain. Reverse mutations occurred in the excision-deficient strain (D7 rad 3), even at low doses of cisplatin. These results are discussed in relation to the possible mechanisms of cisplatin-induced cell death and genotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cisplatin / pharmacology*
  • Cisplatin / toxicity
  • Cross-Linking Reagents
  • DNA Repair / drug effects
  • Gene Conversion / drug effects
  • Mutation / drug effects*
  • Saccharomyces cerevisiae / drug effects*

Substances

  • Cross-Linking Reagents
  • Cisplatin