Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains

Nature. 1980 Dec 25;288(5792):724-7. doi: 10.1038/288724a0.

Abstract

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).

MeSH terms

  • Adenoviruses, Human / genetics
  • Cells, Cultured
  • DNA Repair*
  • Guanine / analogs & derivatives
  • Humans
  • Methylation
  • Methylnitronitrosoguanidine / pharmacology
  • Neoplasms / physiopathology*
  • Simian virus 40*
  • Sister Chromatid Exchange / drug effects

Substances

  • Methylnitronitrosoguanidine
  • Guanine