Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines.
1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links.
Hata
H
H
Research Institute for Tuberculosis and Cancer, Tohoku University, Sendai, Japan.
Numata
M
M
Tohda
H
H
Yasui
A
A
Oikawa
A
A
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005816:Genetic Complementation Test; D066298:In Vitro Techniques; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D015376:Nimustine / Q000378:metabolism / Q000494:pharmacology*; D014466:Ultraviolet Rays; D014965:X-Rays
D008937:Mitomycins; D015376:Nimustine; D016685:Mitomycin; D002945:Cisplatin