title: UVA photoirradiation of benzo[a]pyrene metabolites: induction of cytotoxicity, reactive oxygen species, and lipid peroxidation.
abstract: Benzo[a]pyrene (BaP) is a prototype for studying carcinogenesis of polycyclic aromatic hydrocarbons (PAHs). We have long been interested in studying the phototoxicity of PAHs. In this study, we determined that metabolism of BaP by human skin HaCaT keratinocytes resulted in six identified phase I metabolites, for example, BaP trans-7,8-dihydrodiol (BaP t-7,8-diol), BaP t-4,5-diol, BaP t-9,10-diol, 3-hydroxybenzo[a]pyrene (3-OH-BaP), BaP (7,10/8,9)tetrol, and BaP (7/8,9,10)tetrol. The photocytotoxicity of BaP, 3-OH-BaP, BaP t-7,8-diol, BaP trans-7,8-diol-anti-9,10-epoxide (BPDE), and BaP (7,10/8,9)tetrol in the HaCaT keratinocytes was examined. When irradiated with 1.0 J/cm(2) UVA light, these compounds when tested at doses of 0.1, 0.2, and 0.5 μM, all induced photocytotoxicity in a dose-dependent manner. When photoirradiation was conducted in the presence of a lipid (methyl linoleate), BaP metabolites, BPDE, and three related PAHs, pyrene, 7,8,9,10-tetrahydro-BaP trans-7,8-diol, and 7,8,9,10-tetrahydro-BaP trans-9,10-diol, all induced lipid peroxidation. The formation of lipid peroxides by BaP t-7,8-diol was inhibited by NaN3 and enhanced by deuterated methanol, which suggests that singlet oxygen may be involved in the generation of lipid peroxides. The formation of lipid hydroperoxides was partially inhibited by superoxide dismutase (SOD). Electron spin resonance spin trapping experiments indicated that both singlet oxygen and superoxide radical anion were generated from UVA photoirradiation of BPDE in a light dose responding manner.
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Qingsu
authors.initials: Q
authors.lastname: Xia
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA Department of Cosmecutics, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Chiang
authors.affiliation: Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD, USA.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yin
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Biotranex LLC, Monmouth Junction, NJ, USA.
authors.forename: Lining
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA peter.fu@fda.hhs.gov.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Fu
mesh_terms: D001564:Benzo(a)pyrene / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene
keywords: Benzo[a]pyrene; Polycyclic aromatic hydrocarbons (PAHs); lipid peroxidation; metabolite; reactive oxygen species (ROS)