Skin tumor promotion by Vitamin E in mice: amplification by ionizing radiation and Vitamin C.
We have shown previously that Vitamin E acts as a tumor promoter in 7,12-dimethylbenz(a)anthracene (DMBA) initiated mouse skin. We now show that high concentrations (80 micromol) of Vitamin E are required for promotion, and that 10-fold lower concentrations do not promote tumor formation. The same high concentration of the water-soluble anti-oxidant Vitamin C did not act as a tumor promoter, but did amplify the promoting effect of high, but not low, concentrations of Vitamin E. Oxidizing free radicals generated by beta-radiation exposure of the skin at the time of Vitamin E treatment also enhanced promotion by high (but not low) concentrations of Vitamin E. The results are consistent with a process whereby tumor promotion by the lipid-soluble Vitamin E occurs as a result of alpha-tocopherol acting as a free radical scavenger, with the formation and subsequent transfer of the alpha-tocopherol free radical center to the surrounding lipids, resulting in lipid oxidations.
Mitchel
R E J
RE
Chalk River Laboratories, Radiation Biology and Health Physics Branch, Atomic Energy of Canada Limited, Chalk River, Ont., Canada KOJ 1JO. mitchelr@aecl.ca
McCann
R A
RA
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D001205:Ascorbic Acid / Q000633:toxicity*; D001610:Beta Particles; D002273:Carcinogens / Q000633:toxicity; D003043:Cocarcinogenesis; D005260:Female; D016166:Free Radical Scavengers; D051379:Mice; D018632:Mice, Inbred SENCAR; D010084:Oxidation-Reduction; D011839:Radiation, Ionizing; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D014810:Vitamin E / Q000633:toxicity*
D000975:Antioxidants; D002273:Carcinogens; D016166:Free Radical Scavengers; D014810:Vitamin E; D015127:9,10-Dimethyl-1,2-benzanthracene; D001205:Ascorbic Acid