title: Benzo[a]pyrene and its metabolites combined with ultraviolet A synergistically induce 8-hydroxy-2'-deoxyguanosine via reactive oxygen species.
abstract: We previously reported that benzo[a]pyrene (BaP) and UVA radiation synergistically induced oxidative DNA damage via 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in vitro. The present study shows that microsomal BaP metabolites and UVA radiation potently enhance 8-OHdG formation in calf thymus DNA about 3-fold over the parent compound BaP. Utilization of various reactive oxygen species scavengers revealed that singlet oxygen and superoxide radical anion were involved in the 8-OHdG formation induced by microsomal BaP metabolites and UVA. Two specific BaP metabolites, benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (+/-) (anti) (BPDE) and BaP-7,8-dione, were further tested for synergism with UVA. BaP-7,8-dione showed an effect on 8-OHdG formation induced by UVA radiation that was similar to that of the parent BaP, whereas BPDE exhibited significantly higher induction of 8-OHdG than BaP. At as low as 0.5 microM, BPDE plus UVA radiation substantially increased 8-OHdG levels about 25-fold over the parent BaP. BPDE increased the formation of 8-OHdG levels in both BPDE concentration- and UVA dose-dependent manners. Additionally, singlet oxygen was found to play a major role in 8-OHdG induction by BPDE and UVA. These results suggest that BaP metabolites such as BPDE synergize with UVA radiation to produce ROS, which in turn induce DNA damage.
authors.affiliation: Department of Dermatology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1047, New York, NY 10029, USA.
authors.forename: Dayuan
authors.initials: D
authors.lastname: Gao
authors.forename: Yunjing
authors.initials: Y
authors.lastname: Luo
authors.forename: Denise
authors.initials: D
authors.lastname: Guevara
authors.forename: Yongyin
authors.initials: Y
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Rui
authors.forename: Billie
authors.initials: B
authors.lastname: Goldwyn
authors.forename: Yuhun
authors.initials: Y
authors.lastname: Lu
authors.forename: Elizabeth C A
authors.initials: EC
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Huachen
authors.initials: H
authors.lastname: Wei
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001580:Benzopyrenes / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D026082:Singlet Oxygen / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D001580:Benzopyrenes; D017382:Reactive Oxygen Species; D013481:Superoxides; D026082:Singlet Oxygen; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C076588:benzo(a)pyrene-7,8-dione; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C427203:calf thymus DNA; D003849:Deoxyguanosine