Ethanol and aloe emodin alter the p53 mutational spectrum in ultraviolet radiation-induced murine skin tumors.
Mutations in the p53 tumor-suppressor gene contribute to the development of skin cancer, and the spectrum of mutations in this gene correlates with specific physical and chemical carcinogens in the environment. Cosmetics may contain alcohols and/or aloe emodin (AE). Although these compounds are not carcinogenic when applied to the skin, they may increase the carcinogenicity of ultraviolet (UV) radiation. We investigated whether ethanol (EtOH) and AE alone or combined with UV radiation cause mutations in the p53 gene. In the absence of UV radiation, C3H/HeN mice chronically treated for up to 33 wk with AE in 25% EtOH-in-water vehicle or vehicle alone failed to develop tumors and had no mutations in exons 4-8 of the p53 gene. UV radiation alone induced skin tumors, which had mutations predominantly in p53 exons 5 and 8. In contrast, mutations arising in UV + EtOH-or UV + AE-treated groups were more broadly distributed throughout the p53 gene. Mutations were found in exons 4, 6, and 7, as well as in exons 5 and 8. This altered distribution of mutations across the p53 DNA sequence more closely resembles the pattern observed in TP53 from human skin tumors at sun-exposed sites than that in the p53 gene of mice treated with UV alone. Thus, treatment with UV radiation in combination with two chemicals not thought to be carcinogenic, alcohol, and AE results in a broader distribution of mutations in a critical tumor-suppressor gene.
Department of Immunology, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA.
Donna B
DB
Badgwell
Christopher M
CM
Walker
Whitney T
WT
Baker
Faith M
FM
Strickland
D000818:Animals; D000880:Anthraquinones; D001483:Base Sequence; D017931:DNA Primers; D004642:Emodin / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D016158:Genes, p53; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays
D000880:Anthraquinones; D017931:DNA Primers; D000431:Ethanol; C518327:aloe emodin; D004642:Emodin