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

Julian A. Simon, Philippe Szankasi, Di K. Nguyen, Catherine Ludlow, Heather M. Dunstan, Christopher J. Roberts, Elizabeth L. Jensen, Leland Hartwell, Stephen H. Friend

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)328-333
Number of pages6
JournalCancer Research
Volume60
Issue number2
StatePublished - Jan 15 2000
Externally publishedYes

Fingerprint

DNA Repair
Antineoplastic Agents
Saccharomyces cerevisiae
Cell Cycle Checkpoints
Cytotoxins
Neoplasms
Chromosome Segregation
Mutation
Poisons
DNA
United States Food and Drug Administration
Eukaryota
DNA Damage
Yeasts
X-Rays
Drug Therapy
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Simon, J. A., Szankasi, P., Nguyen, D. K., Ludlow, C., Dunstan, H. M., Roberts, C. J., ... Friend, S. H. (2000). Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. Cancer Research, 60(2), 328-333.

Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. / Simon, Julian A.; Szankasi, Philippe; Nguyen, Di K.; Ludlow, Catherine; Dunstan, Heather M.; Roberts, Christopher J.; Jensen, Elizabeth L.; Hartwell, Leland; Friend, Stephen H.

In: Cancer Research, Vol. 60, No. 2, 15.01.2000, p. 328-333.

Research output: Contribution to journalArticle

Simon, JA, Szankasi, P, Nguyen, DK, Ludlow, C, Dunstan, HM, Roberts, CJ, Jensen, EL, Hartwell, L & Friend, SH 2000, 'Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae', Cancer Research, vol. 60, no. 2, pp. 328-333.
Simon JA, Szankasi P, Nguyen DK, Ludlow C, Dunstan HM, Roberts CJ et al. Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. Cancer Research. 2000 Jan 15;60(2):328-333.
Simon, Julian A. ; Szankasi, Philippe ; Nguyen, Di K. ; Ludlow, Catherine ; Dunstan, Heather M. ; Roberts, Christopher J. ; Jensen, Elizabeth L. ; Hartwell, Leland ; Friend, Stephen H. / Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. In: Cancer Research. 2000 ; Vol. 60, No. 2. pp. 328-333.
@article{0de1e055a5734fb38d27ecfafd0177ec,
title = "Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae",
abstract = "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.",
author = "Simon, {Julian A.} and Philippe Szankasi and Nguyen, {Di K.} and Catherine Ludlow and Dunstan, {Heather M.} and Roberts, {Christopher J.} and Jensen, {Elizabeth L.} and Leland Hartwell and Friend, {Stephen H.}",
year = "2000",
month = "1",
day = "15",
language = "English (US)",
volume = "60",
pages = "328--333",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae

AU - Simon, Julian A.

AU - Szankasi, Philippe

AU - Nguyen, Di K.

AU - Ludlow, Catherine

AU - Dunstan, Heather M.

AU - Roberts, Christopher J.

AU - Jensen, Elizabeth L.

AU - Hartwell, Leland

AU - Friend, Stephen H.

PY - 2000/1/15

Y1 - 2000/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034650849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034650849&partnerID=8YFLogxK

M3 - Article

VL - 60

SP - 328

EP - 333

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 2

ER -