Benzo[a]pyrene enhances the formation of 8-hydroxy-2'-deoxyguanosine by ultraviolet A radiation in calf thymus DNA and human epidermoid carcinoma cells.
The objective of this study is to investigate if benzo[a]pyrene (BaP) and ultraviolet (UV) radiation synergistically induce oxidative DNA damage. Calf thymus DNA was incubated with BaP and irradiated with UVB (280-320 nm) and UVA (335-400 nm). BaP substantially enhanced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) by UVA, but only moderately increased the level of 8-OHdG by UVB. Formation of 8-OHdG proportionally correlated with both UV dose and BaP concentration. Human epidermoid carcinoma cells were incubated with 10 microg of BaP/mL for 24 h and then exposed to 10 kJ/m2 UVB and 25 kJ/m2 UVA. UVB plus BaP did not affect the level of 8-OHdG in cultured cells, whereas UVA plus BaP substantially increased 8-OHdG by over 4-fold compared to BaP and UVA controls. To confirm what reactive oxygen species (ROS) are involved in BaP plus UVA-induced oxidative DNA damage, less or more specific ROS quenchers were added to DNA solution. The results showed that only superoxide dismutase and genistein significantly quenched BaP plus UVA-induced 8-OHdG, whereas catalase, sodium azide, and mannitol exhibited no effect. Our studies suggest that BaP enhances the formation of 8-OHdG in purified DNA and cultured cells by UVA, but not by UVB, and that superoxide anion plays an important role in the synergistic induction of oxidative DNA damage.
Department of Dermatology, Community Medicine and Radiation Oncology, Mount Sinai School of Medicine, New York 10029, USA.
Z
Z
Liu
Y
Y
Lu
B
B
Rosenstein
M
M
Lebwohl
H
H
Wei
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D004247:DNA / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D013950:Thymus Gland; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine