CARCINOGEN BIOACTIVATION AND NEOPLASIA IN PLANARIA

在涡虫中，肿瘤是由化学致癌物(包括

Tumors are induced in planaria by chemical carcinogens (including polycyclic aromatic hydrocarbons and cadmium). In addition, cadmium-induced tumorigenesis in planaria is promoted by phorbol ester treatment. The malignant nature of these tumors was unequivocally demonstrated by light and electron microscopic evaluation and by transplantation experiments. Because these malignancies develop in a relatively short period of time, are readily observed, and these inverbebrate organisms are readily and inexpensively cultured; planaria may represent an attractive non-mammalian model system for carcinogenesis studies. Previous research indicates that tumors can be induced in planaria by procarcinogens that require bioactivation. There is also limited but promising evidence that planaria have enzymatic xenobiotic biotransformation activities. In order to assess the extent of applicability of planaria in carcinogenicity studies, it is important to 1) test a broader range of carcinogens in this system and 2) define the nature of carcinogen-bioactivating enzyme systems in planaria. The proposed project will utilize procarcinogens that are bioactivated by a variety of pathways in mammals. The initial phase of the project will involve in vivo bioassays of carcinogens in Dugesia dorotocephala. Treatments that promote tumor development in planaria will be used to enhance the neoplastic response. Those agents found to induce malignant tumors will be tested for covalent binding to DNA and biotransformation in D. dorotocephala. Procarcinogens to be tested will include polycyclic aromatic hydrocarbons, nitrosamines, aromatic and heterocyclic amines and mycotoxins. Direct-acting carcinogens will also be utilized for comparative purposes. The results of these studies will provide a basis for evaluation of the potential for use of D. dorotocephala in studies of chemical carcinogenicity. The establishment of an invertebrate carcinogenesis model would be an important advance in the field.