Cross-sensitivity of gamma-ray-sensitive hamster mutants to cross-linking agents.
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).
National Institute of Medical Research, Genetics Division, Mill Hill, London, Great Britain.
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K
Caldecott
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P
Jeggo
D000818:Animals; D016466:CHO Cells; D002166:Camptothecin / Q000633:toxicity*; D002460:Cell Line / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D003432:Cross-Linking Reagents / Q000633:toxicity*; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D006168:Guinea Pigs; D008466:Mechlorethamine / Q000633:toxicity; D008558:Melphalan / Q000633:toxicity; D016685:Mitomycin / Q000633:toxicity; D009154:Mutation; D011836:Radiation Tolerance; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D008466:Mechlorethamine; D016685:Mitomycin; D002945:Cisplatin; D008558:Melphalan; D002166:Camptothecin