title: Hydrolysis of carcinogen--DNA adducts by three classes of deoxyribonucleosidase to their corresponding bases.
abstract: We have investigated three different enzymes, each of which splits the glycosidic bonds of normal deoxyribonucleosides, for their ability to cleave acid-sensitive carcinogen-DNA adducts: Leishmania donovani purine deoxyribonucleosidase; Lactobacillus helveticus trans-N-deoxyribosylase; and purine nucleoside phosphorylase. Twenty-eight substrates were assayed using one or more of the enzymes, monitoring free base formation by reverse-phase HPLC and a diode array detector. Products were characterized by their retention times and UV spectra. The deoxyribonucleosidase showed the broadest specificity: substrates cleaved by either the trans-N-deoxyribosylase or the phosphorylase were hydrolyzed by the deoxyribonucleosidase. O6- and N2-alkyldeoxyguanosine, N6-alkyl deoxyadenosine and several cyclic adducts were all hydrolyzed by the deoxyribonucleosidase. None of these enzymes cleaved three bulkier adducts; N2-, N6- and C-8 derivatives of benzo[a]pyrene, benzo[c]phenanthrene and N-acetoxy-2-acetylaminofluorene, respectively. Only the deoxyribonucleosidase hydrolyzed O6-methyldeoxyguanosine while both the deoxyribonucleosidase and trans-N-deoxyribosylase cleaved N6-methyl deoxyadenosine. These enzymes, especially the deoxyribonucleosidase, provide mild ways to release the carcinogen-modified base from deoxyribose and will be useful in DNA adducts analysis.
authors.affiliation: Division of Environmental Science, Columbia University, New York, NY 10032.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Dong
authors.forename: A M
authors.initials: AM
authors.lastname: Jeffrey
mesh_terms: D000478:Alkylation; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000494:pharmacology*; D006868:Hydrolysis; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D002273:Carcinogens; D004247:DNA; D003851:Deoxyribonucleases