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Characterization of Two CHO Variants in Respect to MNNG-Induced Cell Killing, Mutations, and Repair of Methylated DNA Bases

  • R. Goth-Goldstein
  • M. Hughes
Part of the NATO ASI Series book series (NSSA, volume 124)

Abstract

Two Chinese hamster ovary (CHO) cell variants differ substantially in their sensitivity to N-methyl-N’ -nitro-N-nitrosoguanidine (MNNG). The resistant clone (Cl 3) was isolated from the sensitive parent line (Cl 9) after treating Cl 9 cells with a highly cytotoxic dose of MNNG. In contrast to their different sensitivity to the toxic effect of MNNG, the two variants are equally sensitive to its mutagenic effect. MNNG methylates DNA of Cl 9 and Cl 3 to the same extent. Loss of the two methylated purines N3-methyladenine and N7-methylguanine from DNA occurs at the same rate. O6 -methylguanine is not repaired in either clone. We conclude that the increased resistance of Cl 3 is neither due to a reduced uptake or binding of MNNG, nor due to an increased repair of the major methylated bases in DNA.

Keywords

Methylene Blue Chinese Hamster Ovary Cell Chinese Hamster Ovary Xeroderma Pigmentosum Plastic Tissue Culture Flask 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    B. Singer, N-nitroso alkylating agents: formation and persistence of alkyl derivatives in mammalian nucleic acids as contributing factors in carcinogenesis, J. Natl. Cancer Inst. 62:1329–1339(1979).PubMedGoogle Scholar
  2. 2.
    A. E. Pegg, Formation and metabolism of alkylated nucleosides: Possible role in carcinogenesis by nitroso compounds and alkylating agents, Adv. Cancer Res. 25:195–269 (1977).PubMedCrossRefGoogle Scholar
  3. 3.
    P. Karran, T. Lindahl, T. Ofsteng, G. B. Evensen, and E. Seeberg, Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase, J. Mol. Biol. 140:101–127 (1980).PubMedCrossRefGoogle Scholar
  4. 4.
    P. Karran, T. Hjelmgren, and T. Lindahl, Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agents, Nature 296:770–773 (1982).PubMedCrossRefGoogle Scholar
  5. 5.
    D. T. Beranek, R. H. Heflich, R. L. Kodell, S. M. Morris, and D. A. Casciano, Correlation between specific DNA methylation products and mutation induction at the HGPRT locus in Chinese hamster ovary cells, Mutation Res. 110:171–180 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    R. S. Day, III, C. H. J. Ziolkowski, D. A. Scudiero, S. A. Meyer, A. S. Lubiniecki, A. J. Giradi, S. M. Galloway, and G. D. Bynum, Defective repair of alkylated DNA by human tumor and SV40-transformed human cell strain, Nature 288:724–727 (1980).PubMedCrossRefGoogle Scholar
  7. 7.
    R. D. Wood and H. J. Burki, Repair capability and the cellular age response for killing and mutation induction after UV, Mutation Res. 95:505–514 (1982).PubMedCrossRefGoogle Scholar
  8. 8.
    R. Goth-Goldstein, Repair of DNA damaged by alkylating carcinogens is defective in xeroderma pigmentosum derived fibroblasts, Nature 267:81–82 (1977).PubMedCrossRefGoogle Scholar
  9. 9.
    R. Goth-Goldstein, Inability of Chinese hamster ovary cells to excise O6-alkylguanine, Cancer Res. 40:2623–2624 (1980).PubMedGoogle Scholar
  10. 10.
    R. M. Baker, W. C. Van Voorhis, and L. A. Spencer, HeLa cell variants that differ in sensitivity to monofunctional alkylating agents with independence of cytotoxic and mutagenic response, Proc. Natl. Acad. Sci. (USA) 76:5249–5253 (1979)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • R. Goth-Goldstein
    • 1
  • M. Hughes
    • 1
  1. 1.Biomedical Division, Lawrence Berkeley LaboratoryUniversity of CaliforniaBerkeleyUSA

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