Identification of the major adducts formed by reaction of benzo(a)pyrene diol epoxide with DNA in vitro.
Covalent binding of the benzo[a]pyrene metabolite (+/-)7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to calf thymus DNA was investigated. Enzymatic hydrolysis of the carcinogen-modified DNA and subsequent separation via reversed-phase high-pressure liquid chromatography resulted in the detection and isolation of seven distinct products. High-resolution mass spectrometry indicates that these products are covalent adducts of deoxyguanosine, deoxyadenosine, and deoxycytidine. The deoxyguanosine and deoxyadenosine adducts involve binding between the activated hydrocarbon (benzo[a]pyrene diol epoxide) and exocyclic amino groups of the respective purines.
D000225:Adenine; D000818:Animals; D001580:Benzopyrenes; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D003596:Cytosine; D004247:DNA; D004852:Epoxy Compounds; D006147:Guanine; D066298:In Vitro Techniques; D013058:Mass Spectrometry
D001580:Benzopyrenes; D004852:Epoxy Compounds; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000225:Adenine
Nature. 1964 May 23;202:781-4
14187619
J Biochem. 1964 Feb;55:205-8
14135466
Chem Biol Interact. 1976 Oct 2;15(2):149-64
975399
Proc Natl Acad Sci U S A. 1977 May;74(5):1870-4
266709
Nature. 1977 Oct 20;269(5630):725-7
304179
Science. 1977 Jun 10;196(4295):1199-201
870975
J Am Chem Soc. 1977 Mar 2;99(5):1604-11
839009
J Am Chem Soc. 1977 Mar 30;99(7):2358-9
864141
Science. 1977 Aug 12;197(4304):671-4
877583
J Am Chem Soc. 1977 Jan 5;99(1):258-60
830680
Nature. 1976 Nov 25;264(5584):333-9
1004554
J Am Chem Soc. 1976 Oct 13;98(21):6720-2
972227
Science. 1976 Aug 13;193(4253):592-5
959820
Cancer Res. 1975 Mar;35(3):832-43
1116138
Proc Natl Acad Sci U S A. 1976 Jul;73(7):2311-5
821053
Nature. 1974 Nov 22;252(5481):326-8
4473724
J Am Chem Soc. 1973 Oct 31;95(22):7480-90
4747881
Annu Rev Biochem. 1975;44:79-121
1094923
Proc Natl Acad Sci U S A. 1976 May;73(5):1437-41
1064016
J Am Chem Soc. 1976 Sep 1;98(18):5714-5
956574
Biochem Biophys Res Commun. 1976 Jun 21;70(4):1172-9
942439
Cancer Res. 1975 Mar;35(3):844-50
1116139
Cancer Res. 1969 Jun;29(6):1272-6
5797110