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. 1985 Aug;82(16):5250–5254. doi: 10.1073/pnas.82.16.5250

Selective alkylation of carcinogenic 9-anthryloxirane at the N-3 position of adenine in DNA.

N C Yang, C W Chang
PMCID: PMC390545  PMID: 3860860

Abstract

Carcinogenic 9-anthryloxirane binds covalently to calf thymus DNA and poly(dA-dT). Application of the technique for DNA sequence determination shows that acid cleavage of the modified DNA frees approximately half of the anthryl groups from the DNA. HPLC analysis indicates that an adenine adduct and the glycol derived from 9-anthryloxirane are the major acid-labile products. Spectroscopic analyses establish that the adenine adduct is the N-3 adduct of 9-anthryloxirane to adenine. Similar analyses of modified poly(dA-dT) indicate that the binding of 9-anthryloxirane takes place selectively at the N-3 position of adenine. The significance of this finding is briefly 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. BOYLAND E., GREEN B., LIU S. L. FACTORS INFLUENCING THE INTERACTION OF POLYCYCLIC HYDROCARBONS AND DEOXYRIBONUCLEIC ACID. Biochim Biophys Acta. 1964 Aug 12;87:652–663. [PubMed] [Google Scholar]
  2. Bigger C. A., Sawicki J. T., Blake D. M., Raymond L. G., Dipple A. Products of binding of 7,12-dimethylbenz(a)anthracene to DNA in mouse skin. Cancer Res. 1983 Dec;43(12 Pt 1):5647–5651. [PubMed] [Google Scholar]
  3. Boyland E., Sims P., Huggins C. Induction of adrenal damage and cancer with metabolites of 7,12-dimethylbenz(a)anthracene. Nature. 1965 Aug 21;207(999):816–817. doi: 10.1038/207816b0. [DOI] [PubMed] [Google Scholar]
  4. Chen F. M. Binding of pyrene to DNA, base sequence specificity and its implication. Nucleic Acids Res. 1983 Oct 25;11(20):7231–7250. doi: 10.1093/nar/11.20.7231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DiGiovanni J., Slaga T. J., Boutwell R. K. Comparison of the tumor-initiating activity of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene in female SENCAR and CS-1 mice. Carcinogenesis. 1980 May;1(5):381–389. doi: 10.1093/carcin/1.5.381. [DOI] [PubMed] [Google Scholar]
  6. HUGGINS C., YANG N. C. Induction and extinction of mammary cancer. A striking effect of hydrocarbons permits analysis of mechanisms of causes and cure of breast cancer. Science. 1962 Jul 27;137(3526):257–262. doi: 10.1126/science.137.3526.257. [DOI] [PubMed] [Google Scholar]
  7. Hemminki K., Paasivirta J., Kurkirinne T., Virkki L. Alkylation products of DNA bases by simple epoxides. Chem Biol Interact. 1980 Jun;30(3):259–270. doi: 10.1016/0009-2797(80)90049-6. [DOI] [PubMed] [Google Scholar]
  8. Jeffrey A. M., Grzeskowiak K., Weinstein I. B., Nakanishi K., Roller P., Harvey R. G. Benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide adenosine and deoxyadenosine adducts: structure and stereochemistry. Science. 1979 Dec 14;206(4424):1309–1311. doi: 10.1126/science.316186. [DOI] [PubMed] [Google Scholar]
  9. Jensen D. E. Reaction of DNA with alkylating agents. Differential alkylation of poly[dA-dT[ by methylnitrosourea and ethylnitrosourea. Biochemistry. 1978 Nov 28;17(24):5108–5113. doi: 10.1021/bi00617a006. [DOI] [PubMed] [Google Scholar]
  10. Kakefuda T., Yamamoto H. Modification of DNA by the benzo[a]pyrene metabolite diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Proc Natl Acad Sci U S A. 1978 Jan;75(1):415–419. doi: 10.1073/pnas.75.1.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lawley P. D., Jarman M. Alkylation by propylene oxide of deoxyribonucleic acid, adenine, guanosine and deoxyguanylic acid. Biochem J. 1972 Feb;126(4):893–900. doi: 10.1042/bj1260893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LePecq J. B., Paoletti C. A fluorescent complex between ethidium bromide and nucleic acids. Physical-chemical characterization. J Mol Biol. 1967 Jul 14;27(1):87–106. doi: 10.1016/0022-2836(67)90353-1. [DOI] [PubMed] [Google Scholar]
  13. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Osborne M. R., Jacobs S., Harvey R. G., Brookes P. Minor products from the reaction of (+) and (-) benzo[a]-pyrene-anti-diolepoxide with DNA. Carcinogenesis. 1981;2(6):553–558. doi: 10.1093/carcin/2.6.553. [DOI] [PubMed] [Google Scholar]
  15. Singer B., Kröger M., Carrano M. O2- and O4-alkyl pyrimidine nucleosides: stability of the glycosyl bond and of the alkyl group as a function of pH. Biochemistry. 1978 Apr 4;17(7):1246–1250. doi: 10.1021/bi00600a018. [DOI] [PubMed] [Google Scholar]
  16. Straub K. M., Meehan T., Burlingame A. L., Calvin M. Identification of the major adducts formed by reaction of benzo(a)pyrene diol epoxide with DNA in vitro. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5285–5289. doi: 10.1073/pnas.74.12.5285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Watabe T., Ishizuka T., Isobe M., Ozawa N. A 7-hydroxymethyl sulfate ester as an active metabolite of 7,12-dimethylbenz[alpha]anthracene. Science. 1982 Jan 22;215(4531):403–405. doi: 10.1126/science.6800033. [DOI] [PubMed] [Google Scholar]
  18. Weinstein I. B., Jeffrey A. M., Jennette K. W., Blobstein S. H., Harvey R. G., Harris C., Autrup H., Kasai H., Nakanishi K. Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo. Science. 1976 Aug 13;193(4253):592–595. doi: 10.1126/science.959820. [DOI] [PubMed] [Google Scholar]
  19. Yang N. C., Hrinyo T. P., Petrich J. W., Yang D. D. Base sequence selectivity in binding of aromatic hydrocarbons with synthetic polynucleotides. Biochem Biophys Res Commun. 1983 Jul 18;114(1):8–13. doi: 10.1016/0006-291x(83)91586-3. [DOI] [PubMed] [Google Scholar]

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