Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains.
We have identified a group of 8 (among 39) human tumour cell strains deficient in the ability to support the growth of adenovirus 5 preparations treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but able to support the growth of non-treated adenovirus normally. This deficient behaviour defines the Mer- phenotype. Strains having the Mer- phenotype were found to arise from tumours originating in four different organs. Relative to Mer+ strains, Mer- tumour strains showed greater sensitivity to MNNG-produced killing, greater MNNG-stimulated "DNA repair synthesis and a more rapid MNNG-produced decrease in semi-conservative DNA synthesis. Here we report that (1) Mer- strains are deficient in removing O6-methylguanine (O6-MeG) from their DNA after [Me-14C]MMNG treatment (Table 1); (2) Mer- tumour strains originate from tumours arising in patients having Mer+ normal fibroblasts (Fig. 1a, b); (3) SV40 transformation of (Mer+) human fibroblasts often converts them to Mer- strains (Fig. 1c, d); (4) MNNG produces more sister chromatid exchanges (SCEs) in Mer- than in Mer+ cell strains (Fig. 2).
D000260:Adenoviruses, Human / Q000235:genetics; D002478:Cells, Cultured; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives; D006801:Humans; D008745:Methylation; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009369:Neoplasms / Q000503:physiopathology*; D013539:Simian virus 40; D012854:Sister Chromatid Exchange / Q000187:drug effects
D008769:Methylnitronitrosoguanidine; D006147:Guanine