Cross-sensitivity of gamma-ray-sensitive hamster mutants to cross-linking agents

Mutat Res. 1991 Sep;255(2):111-21. doi: 10.1016/0921-8777(91)90046-r.

Abstract

A range of hamster cell mutants, which have been characterised as sensitive to ionising radiation, were examined for their cross-sensitivity to four DNA-DNA cross-linking agents and the protein-DNA cross-linking agent, camptothecin. The mutants represent 7 distinct complementation groups. Two complementation groups were identified as having a major sensitivity to cross-linking damage, more marked than their sensitivity to ionising radiation (irs1, irs1SF). These two mutants also show sensitivity to UV-irradiation. Two of the remaining complementation groups (xrs and XR-1) have a defect in rejoining DNA double-strand breaks, and these exhibit sensitivity to 3 of the 4 DNA-DNA cross-linking agents. The results with these mutants suggest an involvement of double-strand break rejoining in the repair of certain cross-link damage. Two mutants were also notably sensitive to the topoisomerase I inhibiting anticancer drug, camptothecin. One of these mutants was sensitive to the DNA cross-linking agents examined (irs1SF), but the other was not at all sensitive to this class of drug (EM9).

MeSH terms

  • Animals
  • CHO Cells
  • Camptothecin / toxicity*
  • Cell Line / drug effects
  • Cell Line / radiation effects
  • Cell Survival / drug effects
  • Cisplatin / toxicity
  • Cricetinae
  • Cricetulus
  • Cross-Linking Reagents / toxicity*
  • DNA Damage* / radiation effects
  • Female
  • Guinea Pigs
  • Mechlorethamine / toxicity
  • Melphalan / toxicity
  • Mitomycin / toxicity
  • Mutation*
  • Radiation Tolerance
  • Ultraviolet Rays

Substances

  • Cross-Linking Reagents
  • Mechlorethamine
  • Mitomycin
  • Cisplatin
  • Melphalan
  • Camptothecin