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

Nature volume 288, pages 724–727 (1980)Cite this article

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 normally1,2. This deficient behaviour defines the Mer− phenotype2. 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 synthesis2. Here we report that (1) Mer− strains are deficient in removing O6-methylguanine (O6-MeG) from their DNA after [Me-14C]MNNG 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).

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Authors and Affiliations

  1. Nucleic Acids Section, LMC, CIP, DCCP, NCI, NIH, 9000 Rockville Pike, Bethesda, Maryland, 20205

    Rufus S. Day III & Chuck H. J. Ziolkowski

  2. Chemical Carcinogenesis Program, Frederick Cancer Research Center, Frederick, Maryland, 21701

    Dominic A. Scudiero & Sharon A. Meyer

  3. Flow Laboratories, 7655 Old Spring House Road, McLean, Virginia, 22101

    Anthony S. Lubiniecki

  4. Institute for Medical Research, Copewood and Davis Streets, Camden, New Jersey, 08103

    Anthony J. Girardi

  5. Litton Bionetics, 5516 Nicholson Lane, Kensington, Maryland, 20795

    Sheila M. Galloway

  6. Section on Cellular Aging, Laboratory of Comparative Cellular Physiology, Gerontology Research Center, NIA, Baltimore, Maryland, 21224

    Gaither D. Bynum

Authors
  1. Rufus S. Day III
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  2. Chuck H. J. Ziolkowski
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  8. Gaither D. Bynum
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Day, R., Ziolkowski, C., Scudiero, D. et al. Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains. Nature 288, 724–727 (1980). https://doi.org/10.1038/288724a0

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