title: Effects of UV light and tumor promoters on endogenous vitamin E status in mouse skin.
abstract: Recent reports indicate that both orally administered and topically applied alpha-tocopherol (vitamin E, TH) prevent UVB-induced skin carcinogenesis in mice. Because UVB exposure causes the formation of oxidants associated with tumor promotion, epidermal TH status may be an important determinant of susceptibility to photocarcinogenesis. To test this hypothesis, we studied the status of epidermal TH in C3H mice following exposure to single and repeated UVB exposures at doses typical of chronic photocarcinogenesis protocols. Exposure of mice to a single 13 kJ/m(2) dose over 60 min resulted in no acute depletion of epidermal TH and a modest increase in TH within 6-12 h. Daily exposure to 6.5 kJ/m(2) over 30 min resulted in a gradual increase in epidermal TH, which reached 5-fold after five daily exposures. The increase in epidermal TH was accompanied by an increase in the TH oxidation products alpha-tocopherolquinone (TQ) and alpha-tocopherolhydroquinone (THQ). We also studied the effect of the prooxidant chemical tumor promoter benzoyl peroxide and the prooxidant azo initiators azobis(amidinopropane HCl) and azobis(2, 4-dimethylvaleronitrile). Topical application of these prooxidant chemicals acutely oxidized epidermal TH to TQ and THQ. Topical treatments with the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increased epidermal TH levels without producing a significant accumulation of TH oxidation products. The results indicate that UVB and tumor promoting chemicals all exert qualitatively different effects on epidermal TH status and that UVB and TPA trigger an adaptive response involving epidermal TH accumulation.
authors.affiliation: Department of Pharmacology and Toxicology and Southwest Environmental Health Sciences Center, College of Pharmacy, The University of Arizona, Tucson, AZ 85721-0207, USA. liebler@pharmacy.arizona.edu
authors.forename: D C
authors.initials: DC
authors.lastname: Liebler
authors.forename: J A
authors.initials: JA
authors.lastname: Burr
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001391:Azo Compounds / Q000494:pharmacology; D001585:Benzoyl Peroxide / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D003043:Cocarcinogenesis; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005260:Female; D006873:Hydroquinones / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress; D010777:Photochemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000031:analogs & derivatives / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
chemical_list: D000578:Amidines; D000975:Antioxidants; D001391:Azo Compounds; D002273:Carcinogens; D006873:Hydroquinones; D009570:Nitriles; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D014810:Vitamin E; C024838:alpha-tocopherol quinol; C046728:2,2'-azobis(2-amidinopropane); C002421:tocopherylquinone; D024502:alpha-Tocopherol; D013755:Tetradecanoylphorbol Acetate; D001585:Benzoyl Peroxide