INITIATION - PROMOTION BIOASSAY IN MOUSE LIVER

该项目的目的是开发和验证一个短期/有限的 在15日龄小鼠中进行的肝启动-促进生物测定， 确定致癌物、肿瘤引发物、肿瘤促进物和 化学预防活性的化学品和复杂的混合物 环境样品。 在第一阶段，我们确定C3 H小鼠 15日龄时对8种化学致癌物中的7种敏感 测试和苯巴比妥促进所需的活动5 在C3 H中有活性的7种致癌物（黄曲霉毒素B1，2-乙酰氨基芴， 联苯胺、DMBA和β-萘胺）。 B6 C3 F1小鼠敏感 八种致癌物中的三种，苯巴比妥抑制了 二乙基亚硝胺引发的肿瘤的发生。 二期将 进一步开发和验证生物测定法，包括：1）表征 参数如品系、性别和溶媒，2）测定 她的化学类别的致癌物，其中该测定是适合的 （灵敏的），3）确定用于结构的测定的用途- 活动关系，4）区分能力的测定 肿瘤引发剂和促进剂，以及5）证明适用性 用于筛选化学预防活性物质。 一旦 开发并验证了肝脏启动促进生物测定法， 日龄小鼠肝脏将提供非常有用的商业测试系统 用于评价化学品和环境的致癌危害 复杂混合物的样品。

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.