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 language | English (US) |
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Pages (from-to) | 1177-83 |
Number of pages | 7 |
Journal | Free Radical Biology and Medicine |
Volume | 39 |
Issue number | 9 |
DOIs | |
State | Published - 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