Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae

Cancer Res. 2000 Jan 15;60(2):328-33.


Most cytotoxic anticancer agents damage DNA directly, interfere with DNA metabolism or chromosome segregation, and are particularly toxic in dividing cells. Although a considerable amount of information on the mechanisms of action of these agents is available, the molecular bases for selective tumor cell killing by chemotherapy are largely unknown. Many genetic alterations found in sporadic and hereditary cancers affect functions in DNA repair and cell cycle control and result in sensitivity to DNA damaging agents. We have therefore set out to determine the effects of these cancer mutations on sensitivity or resistance to various chemotherapeutic agents. Because most of the affected genes are well conserved among eukaryotes, we have carried out a comprehensive analysis of a panel of isogenic yeast strains, each defective in a particular DNA repair or cell cycle checkpoint function, for sensitivity to the Food and Drug Administration-approved cytotoxic anticancer agents. Widely different toxicity profiles were observed for 23 agents and X-rays, indicating that the type of DNA repair and cell cycle checkpoint mutations in individual tumors could strongly influence the outcome of a particular chemotherapeutic regimen.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • DNA Damage
  • DNA Repair / drug effects*
  • DNA Repair / radiation effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / radiation effects
  • United States
  • United States Food and Drug Administration
  • X-Rays


  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents