title: Wavelength dependent responses of primary human keratinocytes to combined treatment with benzo[a]pyrene and UV light.
abstract: The major risk factor for skin cancer is exposure to UV radiation from sunlight, but other environmental exposures may also play a role in combination with UV. We have studied the effects of combined exposure of primary human skin cells in vitro to UVA, UVB or UVC with benzo[a] pyrene (BaP), an environmental carcinogen. Normal human keratinocytes were exposed to 5 microM BaP for 24 h followed by either 1 kJ/m(2) UVA, 100 J/m(2) UVB or 10 J/m(2) UVC. Only BaP + UVA caused increased cell death. BaP or UVA alone did not induce significant DNA damage as measured by comet assay but combined exposure induced 35.1 +/- 6.0% tail DNA, compared with 9.7 +/- 1.3% tail DNA in control cells. After including the Fapy-DNA glycosylase enzyme incubation step to detect oxidized purines, % tail DNA increased another 11.2 +/- 2.9%. Combined exposure of BaP and UVB did not increase damage in the comet assay without Fapy-DNA glycosylase, but in the presence of this enzyme % tail DNA increased by 9.3 +/- 2.2%. BaP + UVB also abrogated the UVB-induced cell cycle G2 arrest. BaP + UVC had no effect on the keratinocytes compared with each treatment alone. These results show a wavelength-dependent difference in the effects of combined exposure on normal human keratinocytes. Both UVA and UVB damage can be enhanced by BaP pre-exposure, although the effects seen with UVA were greater. These findings are important to understanding the role of UVA and UVB in skin carcinogenesis and may have implications for recommended sun exposure limits, especially in polluted areas.
authors.affiliation: Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute for Genetics, Health and Therapeutics and The School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Crallan
authors.forename: Eileen
authors.initials: E
authors.lastname: Ingham
authors.forename: Michael N
authors.initials: MN
authors.lastname: Routledge
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D018384:Oxidative Stress; D012867:Skin / Q000166:cytology; D013472:Sunlight; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D001564:Benzo(a)pyrene