Hybrids between human tumor cell strains differing in repair of MNNG-produced DNA damage.
Human tumor cell strains with differing responses to MNNG damage in their DNA were treated with precipitates of the plasmids pSV2gpt or pSV2neo . Transfected clones were selected on the basis of the drug resistance which each plasmid confers. Cells with different drug resistances were fused and hybrids were selected in medium requiring the expression of both markers. Hybrids produced by fusion of two different strains hypersensitive to MNNG-produced cytotoxicity and which lack the DNA repair enzyme O6-methylguanine-DNA methyltransferase ( O6MT ) failed to show complementation, suggesting that these strains share a common genetic defect. Hybrids from fusions of each of three strains containing O6MT activity with the same strain lacking O6MT activity were of surprising character. In one case the hybrid had resistance to MNNG-produced cell killing and O6MT activity similar to the parent strain possessing O6MT activity. In a second case, the hybrid had greater resistance to MNNG produced cytotoxicity than either parent strain although the level of O6MT activity was not higher. In a third case, the hybrid had little or no O6MT and as great hypersensitivity to MNNG-produced cytotoxicity as the parent strain lacking O6MT activity. We conclude that the survival of human tumor cell strains after MNNG-produced DNA damage is controlled by several genes. Even individual repair enzymes, like O6MT , are likely to be regulated by the interaction of these genes.
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D002999:Clone Cells; D004260:DNA Repair; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects* / Q000502:physiology; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D008780:Methyltransferases / Q000235:genetics; D051379:Mice; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010957:Plasmids; D014162:Transfection
D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase