This proposal seeks to continue funding for the newborn mouse lung adenoma bioassay to provide sensitive, cost-effective evaluation of the tumorigenic activity of pure compounds and effluent extracts related to and derived from fuel combustion. This assay is further distinguished by the small amounts of compounds required for testing since newborn mice are treated with only three injections and by the fact that tumors may be induced at sites other than the lung (liver, lymphatic system). Tumor incidence multiplicity and progression to the neoplastic state will be quantified at three dose levels for eight compounds or materials/year to supplement information obtained from bacterial and human lymphoblast mutation assays to facilitate the assessment of human health risk. Many compounds to be tested will be provided by synthetic chemists at Leiden University (The Netherlands) and will include, but not be limited to, alkyl-, cyclopenta, and nitro-polynuclear aromatic compounds (PAC). The necessity of evaluating the extent of co-carcinogenic or inhibitory interactions between major environmentally significant PAC will be addressed in a series of studies with the newborn mouse assay to: (1) investigate whether the reported co-carcinogenic activity of fluoranthene, pyrene and benzo(e)pyrene in benzo(a)pyrene (BaP) induced mouse skin tumors is also operative in the induction of mouse lung tumors; (2) determine the activity of lung tumorigenic activity among known, potent mouse lung carcinogens such as cyclopenta(c,d)pyrene, BaP, benzo(a)anthracene and benzo(b)fluoranthene; and finally (3) quantitatively measure the effects of the components of an unfractionated extract of pulverized coal combustion effluent on carcinogenic activity by spiking experiments with known amounts of the above compounds.
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