The research proposed here seeks to define the efficacy of the use of orange peel oil as an anticarcinogen while further defining its mechanism of action in this role. To accomplish this HPLC techniques will be used to isolate the components of orange peel oil. The anticarcinogenic potency of these components will be quantitated by feeding them in a totally defined diet to rats exposed to DMBA. Carcinogen specificity will be defined by testing the ability of the orange peel oil anticarcinogen(s) to inhibit both spontaneous and induced mammary tumors. Organ specificity will be examined by testing the ability of the orange peel oil anticarcinogen(s) to inhibit neoplastic changes in mammary gland, skin and bladder. Species specificity studies will compare the response of carcinogen exposed rats and mice to orange oil anticarcinogens. In addition, similar in vitro comparisons will be made using rat and human primary parenchymal cells from mammary gland and liver. Individual specificity will be modeled with rat strains possessing high or low sensitivity to the induction of mammary carcinomas. All animal experiments will be analyzed using both parametric and nonparametric statistical procedures. Once the anticarcinogen is identified its pharmacokinetics and metabolism will be defined. The biological activity of these metabolites will be determined. The mechanism(s) of action of the orange peel oil anticarcinogen(s) and/or its metabolites will be studied.
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