title: Incorporation of two deoxycytidine oxidation products into cellular DNA.
abstract: The oxidation of cytosine in DNA by free radicals and other oxidants leads to an assortment of products including pyrimidine ring 5,6-saturated, 5,6-unsaturated, contraction, and fragmentation products. The formation of these products in cellular DNA may explain in part the preponderance of C to T transitions induced spontaneously and by H2O2 or ionizing radiation. Our studies have focused on the biological effects of two major 5,6-unsaturated oxidation products of cytosine: 5- hydroxycytosine and 5-hydroxyuracil. In the present work, we have attempted to study the repair of these two lesions by specifically incorporating them into cellular DNA upon incubation of cells with 5-hydroxy-2'deoxycytidine and 5-hydroxy-2'-deoxyuridine. Incubation of mouse L1210 cells with 250 M 5-hydroxy-2'-deoxycytidine led to the incorporation of this lesion to a level 20 times higher (43 lesions/10(5) cytosines) than base-line levels; however, there was no evidence for its repair following a 15-h chase. In contrast, we did not observe any significant incorporation of 5-hydroxy-2'-deoxyuridine into the DNA of L1210 cells but did observe an unidentified product, presumably an oxidation product. This unidentified pyrimidine was incorporated at a very high level (about 2000 lesions/10(5) cytosine residues) and then partially repaired in chase experiments.
authors.affiliation: Institut universitaire de gériatrie de Sherbrooke, QC, Canada. rwagner@courrier.usherb.ca
authors.forename: J R
authors.initials: JR
authors.lastname: Wagner
authors.forename: S
authors.initials: S
authors.lastname: Tremblay
authors.forename: B
authors.initials: B
authors.lastname: Gowans
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunting
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007939:Leukemia L1210; D051379:Mice; D010084:Oxidation-Reduction
chemical_list: D003841:Deoxycytidine; C074088:5-hydroxy-2'-deoxyuridine; C074071:5-hydroxy-2'-deoxycytidine; D004247:DNA; D003857:Deoxyuridine