Benzo[a]pyrene and its metabolites combined with ultraviolet A synergistically induce 8-hydroxy-2'-deoxyguanosine via reactive oxygen species

Dayuan Gao, Yunjing Luo, Denise Guevara, Yongyin Wang, Mei Rui, Billie Goldwyn, Yuhun Lu, Elizabeth C A Smith, Mark Lebwohl, Huachen Wei

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1177-83
Number of pages7
JournalFree Radical Biology and Medicine
Volume39
Issue number9
DOIs
StatePublished - Nov 1 2005

Keywords

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/toxicity
  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Benzo(a)pyrene/metabolism
  • Benzopyrenes/toxicity
  • DNA/drug effects
  • DNA Damage
  • Deoxyguanosine/analogs & derivatives
  • Female
  • Mice
  • Mice, Inbred Strains
  • Microsomes/metabolism
  • Reactive Oxygen Species/metabolism
  • Singlet Oxygen/metabolism
  • Superoxides/metabolism
  • Ultraviolet Rays

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