title: 32P-postlabeling analysis of inhibition by norharman of formation of dibenzo[a,e]fluoranthene--DNA adducts in mouse embryo fibroblasts.
abstract: Quantitative and qualitative changes in the inhibition of DNA adduct formation in the presence of increasing concentrations of norharman (NH) were investigated in vivo in mouse fibroblasts treated with dibenzo[a,e]fluoranthene (DBF), a potent carcinogen in mice. The nuclease P1 modification of the 32P-postlabeling technique was used to identify adducts. A dose-dependent reduction in DBF-DNA adduct formation was observed: an 80% reduction with 0.06 mM NH and 90% with 0.12 mM NH. At 0.12 mM NH, all of the spots coming from hydroxylated DBF vicinal dihydrodiol (DHD) epoxides were missing; the only clear spot was that of the major DBF adduct produced by the ultimate DBF metabolite, DBF-3,4-DHD-1,2 oxide. Spots representing other DBF-DHD epoxide adducts appeared only in trace amounts. These results can be interpreted as a dose-dependent competition or inhibition of some secondary metabolic step, most probably secondary epoxidation; however, a direct protective effect of NH during adduct formation cannot be excluded. NH is a strong inhibitor of DBF-DNA adduct formation in vivo.
authors.affiliation: Unité de Recherche sur la Prolifération Cellulaire et la Cancérogénèse, CNRS-URA, Institu Curie, Orsay, France.
authors.forename: O
authors.initials: O
authors.lastname: Périn-Roussel
authors.forename: F
authors.initials: F
authors.lastname: Périn
authors.forename: N
authors.initials: N
authors.lastname: Barat
authors.forename: F
authors.initials: F
authors.lastname: Zajdela
mesh_terms: D000818:Animals; D002243:Carbolines; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005449:Fluorenes / Q000378:metabolism*; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D010761:Phosphorus Radioisotopes; D011247:Pregnancy
chemical_list: D002243:Carbolines; D002273:Carcinogens; D005449:Fluorenes; D010761:Phosphorus Radioisotopes; D006247:Harmine; C012888:dibenzo(a,e)fluoranthene; D004247:DNA; C010262:norharman