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. 1973 Oct;136(2):387–393. doi: 10.1042/bj1360387

Cellular reactions of O6-methylguanine, a product of some alkylating carcinogens

Carolyn Thatcher Miller 1, Philip D Lawley 1, Sudhirkumar A Shah 1
PMCID: PMC1165965  PMID: 4590203

Abstract

Cultures of a purine-requiring mutant of Chinese hamster ovary cells (CHO-104b), randomly bred hamster embryo cells, or Escherichia coli Bs−1 were treated with non-toxic doses of 3H-labelled O6-methylguanine. DNA and RNA were isolated and subjected to enzymic digestion to nucleosides at pH8. The products of digestion were analysed by ion-exchange chromatography on columns of Dowex 50 (NH4+ form) at pH8.9. No 3H-labelled O6-methylguanosine was detected in nucleic acid digests. 3H-labelled O6-methylguanine was O-demethylated yielding [3H]guanine in CHO-104b cells. Radioactivity in nucleic acid digests was associated with thymidine, guanosine, deoxyguanosine and an unidentified early-eluting product. Reports of similar unidentified products from nucleic acids labelled with various agents are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BROWN D. M., TODD A. R. Nucleic acids. Annu Rev Biochem. 1955;24:311–338. doi: 10.1146/annurev.bi.24.070155.001523. [DOI] [PubMed] [Google Scholar]
  2. Bannon P., Verly W. Alkylation of phosphates and stability of phosphate triesters in DNA. Eur J Biochem. 1972 Nov 21;31(1):103–111. doi: 10.1111/j.1432-1033.1972.tb02506.x. [DOI] [PubMed] [Google Scholar]
  3. DULBECCO R., VOGT M. One-step growth curve of Western equine encephalomyelitis virus on chicken embryo cells grown in vitro and analysis of virus yields from single cells. J Exp Med. 1954 Feb;99(2):183–199. doi: 10.1084/jem.99.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Frei J. V. Tissue-dependent differences in DNA methylation products of mice treated with methyl-labelled methylnitrosourea. Int J Cancer. 1971 May 15;7(3):436–442. doi: 10.1002/ijc.2910070309. [DOI] [PubMed] [Google Scholar]
  5. HENDERSON J. F., MAZEL P. DEMETHYLATION OF PURINE ANALOGS BY MICROSOMAL ENZYMES FROM MOUSE LIVER. Biochem Pharmacol. 1964 Feb;13:207–210. doi: 10.1016/0006-2952(64)90138-8. [DOI] [PubMed] [Google Scholar]
  6. KIRBY K. S. A new method for the isolation of deoxyribonucleic acids; evidence on the nature of bonds between deoxyribonucleic acid and protein. Biochem J. 1957 Jul;66(3):495–504. doi: 10.1042/bj0660495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. LEPAGE G. A. BASIC BIOCHEMICAL EFFECTS AND MECHANISM OF ACTION OF 6-THIOGUANINE. Cancer Res. 1963 Sep;23:1202–1206. [PubMed] [Google Scholar]
  8. Lawley P. D., Orr D. J. Specific excision of methylation products from DNA of Escherichia coli treated with N-methyl-N'-nitro-N-nitrosoguanidine. Chem Biol Interact. 1970 Aug;2(2):154–157. doi: 10.1016/0009-2797(70)90047-5. [DOI] [PubMed] [Google Scholar]
  9. Lawley P. D., Shah S. A. Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels. Biochem J. 1972 Jun;128(1):117–132. doi: 10.1042/bj1280117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lawley P. D., Thatcher C. J. Methylation of deoxyribonucleic acid in cultured mammalian cells by N-methyl-N'-nitro-N-nitrosoguanidine. The influence of cellular thiol concentrations on the extent of methylation and the 6-oxygen atom of guanine as a site of methylation. Biochem J. 1970 Feb;116(4):693–707. doi: 10.1042/bj1160693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Loveless A. Possible relevance of O-6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature. 1969 Jul 12;223(5202):206–207. doi: 10.1038/223206a0. [DOI] [PubMed] [Google Scholar]
  12. O'Connor P. J., Capps M. J., Craig A. W. Comparative studies of the hepatocarcinogen N,N-dimethylnitrosamine in vivo: reaction sites in rat liver DNA and the significance of their relative stabilities. Br J Cancer. 1973 Feb;27(2):153–166. doi: 10.1038/bjc.1973.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. O'Connor P. J., Capps M. J., Craig A. W., Lawley P. D., Shah S. A. Differences in the patterns of methylation in rat liver ribosomal ribonucleic acid after reaction in vivo with methyl methanesulphonate and NN-dimethylnitrosamine. Biochem J. 1972 Sep;129(3):519–528. doi: 10.1042/bj1290519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Price D. J., Timson J. 6-thioguanine: antimitotic effect on human lymphocytes in vitro prevented by adenine. Br J Cancer. 1971 Mar;25(1):106–108. doi: 10.1038/bjc.1971.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Taylor M. W., Souhrada M., McCall J. New class of purine mutants of Chinese hamster ovary cells. Science. 1971 Apr 9;172(3979):162–163. doi: 10.1126/science.172.3979.162. [DOI] [PubMed] [Google Scholar]
  16. Wolfenden R., Sharpless T. K., Allan R. Substrate binding by adenosine deaminase. Specificity, pH dependence, and competition by mercurials. J Biol Chem. 1967 Mar 10;242(5):977–983. [PubMed] [Google Scholar]

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