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REACTION OF CYCLOPENTA[CD]PYRENE-3,4-EPOXIDE WITH DNA AND DEOXYNUCLEOTIDES
Citation:
Beach, A., S. Agarwal, G. Lambert, S. Nesnow, AND R. Gupta. REACTION OF CYCLOPENTA[CD]PYRENE-3,4-EPOXIDE WITH DNA AND DEOXYNUCLEOTIDES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/337.
Description:
Cyclopenta[cd]pyrene (CPP) is a ubiquitous polycyclic aromatic hydrocarbon with potent mutagenic and carcinogenic activity. he trans isomer of 3,4-dihydro-3,4-dihydroxy-cyclopenta[cd]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. he direct mutagenicity of CPP-3,4-epo3dde, 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. PP-3,4-epoxide was reacted with calf thymus DNA, dGp, dAp, dTp, dCp, poly dB-dC, poly dA-dT, and poly dG. dducts were analyzed by the butanol-enhanced version of 3P-postlabeling. our major and at least three minor adducts formed with DNA in vitro, which were further analyzed for their base selectivity. imilar spectra of adducts was exhibited by dGp, poly dG-dC and poly dG. dCp, dTp, and dAp formed one, two, and four adducts, respectively. he relative binding in adducts per 101 nucleotides was in the following descending order: dGp (6000), poly dG-dC (5800), dTp (5300), dAp (48W), calf thymus DNA (3800), poly dA-dT (2300), poly dG (2600), and dCp (20). dducts derived from either dGp, poly dG-dC, or poly dG comigirated with the DNA adducts in 3 solvent systems indicating thai CPP-3,4-epoxide forms DNA adducts almost exclusively with deoxyguanosine.