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Tumor promotion by a hydroperoxide metabolite of butylated hydroxytoluene, 2,6-di-tert-butyl-4-hydroperoxy-4-methyl-2,5-cyclohexadienone, in mouse skin. 1988

B G Taffe, and T W Kensler
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205.

The nature of the skin tumor promotion response to a hydroperoxide metabolite of butylated hydroxytoluene, 2,6-di-tert-butyl-4-hydroperoxyl-2,5-cyclohexadienone (BHTOOH), was examined in SENCAR mice. BHTOOH was an effective inducer of epidermal ornithine decarboxylase (ODC) activity. Maximal induction of ODC activity was observed 12 hours after a single application of BHTOOH. Dose-dependent increases were seen between 2 and 20 mumol while higher amounts were less effective. A similar dose-response relationship for papilloma and carcinoma formation was observed when BHTOOH was applied twice weekly for 50 weeks to mice previously initiated with 7,12-dimethylbenz[a]anthracene. Doses of 2, 8, and 20 mumol BHTOOH gave maximal papilloma responses of 0.1, 0.6, and 3.6 papillomas/mouse, respectively. The progression of papillomas to carcinomas was examined and at 60 weeks the incidence of carcinomas was 0, 17, and 28% for the three treatment groups. The carcinoma:papilloma ratios were 0.08 and 0.40 for the high and intermediate BHTOOH dose groups. The data suggest that BHTOOH, unlike butylated hydroxytoluene, is an effective tumor promoter in mouse skin. Additionally, BHTOOH may enhance the conversion of papillomas to carcinomas. However, BHTOOH is not a complete carcinogen in that no papillomas or carcinomas were observed in uninitiated mice treated with BHTOOH only.

UI MeSH Term Description Entries
D009955 Ornithine Decarboxylase A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine. Ornithine Carboxy-lyase,Carboxy-lyase, Ornithine,Decarboxylase, Ornithine,Ornithine Carboxy lyase
D010212 Papilloma A circumscribed benign epithelial tumor projecting from the surrounding surface; more precisely, a benign epithelial neoplasm consisting of villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells. (Stedman, 25th ed) Papilloma, Squamous Cell,Papillomatosis,Papillomas,Papillomas, Squamous Cell,Papillomatoses,Squamous Cell Papilloma,Squamous Cell Papillomas
D010545 Peroxides A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed) Peroxide
D011809 Quinones Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D002084 Butylated Hydroxytoluene A di-tert-butyl PHENOL with antioxidant properties. Butylhydroxytoluene,2,6-Bis(1,1-dimethylethyl)-4-methylphenol,2,6-Di-t-butyl-4-methylphenol,2,6-Di-tert-butyl-4-methylphenol,2,6-Di-tert-butyl-p-cresol,4-Methyl-2,6-ditertbutylphenol,BHT,Di-tert-butyl-methylphenol,Dibunol,Ionol,Ionol (BHT),2,6 Di t butyl 4 methylphenol,2,6 Di tert butyl 4 methylphenol,2,6 Di tert butyl p cresol,4 Methyl 2,6 ditertbutylphenol,Di tert butyl methylphenol,Hydroxytoluene, Butylated
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D003043 Cocarcinogenesis The combination of two or more different factors in the production of cancer. Cocarcinogeneses
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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