||Reaction of Cyclopent(c,d)pyrene-3,4-epoxide with DNA and Deoxynucleotides.
Beach, A. C. ;
Agarwall, S. A. ;
Lambert, G. R. ;
Nesnow, S. ;
Gupta, R. C. ;
||Kentucky Univ., Lexington. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.
Deoxyribonucleic acids ;
DNA damage ;
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||Cyclopenta(c,d)pyrene (CPP) is a ubiquitous polycyclic aromatic hydrocarbon with potent mutagenic and carcinogenic activity. The trans isomer of 3,4-dihydro-3,4-dihydroxy-cyclopenta(c,d)pyrene has been shown to be the major metabolic product of CPP in rat, mouse, or human microsomal systems as well as in peroxyl radical-generating systems indicating the preferential formation of its obligatory precursor, CPP-3,4-epoxide. The direct mutagenicity of CPP-3,4-epoxide, the inactivity of 3,4-dihydro-CPP, and the DNA adduct forming capacity of CPP in vivo has prompted analysis of the DNA adduct forming capacity of CPP-3,4-epoxide to provide information pertaining to: (1) the role this postulated major ultimate mutagenic metabolite may plan in the formation of DNA adducts in vivo; (2) the base selectivity of CPP-3,4-epoxide DNA adducts; and (3) the role of CPP-3,4-epoxide in the mutagenicity/carcinogenicity of CPP. CPP-3,4-epoxide was reacted with calf thymus DNA, dGp, dAp, dTp, dCp, poly dB-dC, poly dA-dT, and poly dG. Adducts were analyzed by the butanol-enhanced version of (32)P-postlabeling. Four major and at least three minor adducts formed with DNA in vitro, which were further analyzed for their base-selectivity. A similar spectra of adducts was exhibited by dGp, poly dG-dC and poly dG. dCp, dTp, and dAp formed one, two, and four adducts, respectively. Adducts derived from either dGp, poly dG-dC, or poly dG comigrated with the DNA adducts in 3 solvent systems indicating that CPP-3,4-epoxide forms DNA adducts almost exclusively with deoxyguanosine.
||Pub. in Jnl. of Carcinogenesis, v14 n4 p767-771 Apr 93. Prepared in cooperation with Environmental Health Research and Testing, Inc., Research Triangle Park, NC. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
|NTIS Title Notes
||Reprint: Reaction of Cyclopent(c,d)pyrene-3,4-epoxide with DNA and Deoxynucleotides.
||PC A02/MF A01