Transfection of DNA from a chloroethylnitrosourea-resistant tumor cell line (MER+) to a sensitive tumor cell line (MER-) results in a tumor cell line resistant to MNNG and CNU that has increased O-6-methylguanine-DNA methyltransferase levels and reduced levels of DNA interstrand crosslinking.
A subclone of a human glioma tumor cell strain which was deficient at O-6-alkylguanine repair was transfected with DNA from an O-6-alkylguanine DNA alkyltransferase-positive human colon tumor cell line (HT29). The transfected subclone, which was selected by its resistance to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), acquired increased resistance to chloroethylnitrosourea (CNU), contained O-6-methylguanine-DNA methyltransferase activity, and failed to accumulate interstrand crosslinks in its DNA upon treatment with CNU. The subclone morphologically resembled its CNU-sensitive parental glioma cell strain. The close correlation between the increased cellular resistance, increased O-6-alkylguanine repair activity and the absence of crosslinking suggests that the formation of DNA crosslinks is one important mechanism of cytotoxicity produced by CNU, and that repair of DNA lesions by O-6-alkylguanine DNA alkyltransferase may partially prevent CNU-induced cytotoxicity.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism*; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D008780:Methyltransferases / Q000032:analysis*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D014162:Transfection
D004273:DNA, Neoplasm; D008769:Methylnitronitrosoguanidine; C017139:1-(2-chloroethyl)-1-nitrosourea; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005038:Ethylnitrosourea