INITIATION - PROMOTION BIOASSAY IN MOUSE LIVER

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The aim of this project is to develop and validate a short-term/limited liver initiation-promotion bioassay in 15 day old mice for use in determination of the carcinogenic, tumor initiating, tumor promoting and chemoprevention activity of chemicals and complex mixture of environmental samples. In Phase I, we determined that C3H mice were sensitive at day 15 of age to seven of the eight chemical carcinogens tested and that phenobarbital promotion was required for activity by 5 of 7 carcinogens active in C3H (aflatoxin B1, 2-acetylaminofluorene, benzidine, DMBA, and beta-naph-thalamine). B6C3F1 mice were sensitive to only three of eight carcinogens and phenobarbital inhibited the occurrence of diethylnitrosamine-initiated tumors. Phase II will further develop and validate the bioassay including, 1) characterization of the parameters such as strain, sex, and vehicle, 2) determination of her chemical classes of carcinogens to which the assay is suitable (sensitive), 3) determination of the use of the assay for structure- activity relationships, 4) determination of the ability to distinguish tumor initiators and promoters, and 5) demonstration of the suitability of the assay to screening substances for chemoprevention activity. Once developed and validated the liver initiation-promotion bioassay in 15 day old mouse liver would provide a very useful commercial test system for evaluation of the carcinogenic hazard of chemicals and environmental samples of complex mixtures.