INITIATION - PROMOTION BIOASSAY IN MOUSE LIVER

该项目的目标是开发和验证短期/有限的 15日龄小鼠肝脏启动促进生物测定法 致癌物、致癌物、促癌物、促癌物和 化学物质和化合物的复杂混合物的化学预防活性 环境样本。在第一阶段，我们确定C3H小鼠是 在15日龄对八种化学致癌物中的七种敏感 进行了测试，并要求在5岁之前促进苯巴比妥的活动 在7种具有C3H活性的致癌物中(黄曲霉毒素B1、2-乙酰氨基荧烯、 联苯胺、DMBA和β-纳巴胺)。B6C3F1小鼠敏感 仅对八种致癌物中的三种和苯巴比妥抑制 二乙基亚硝胺引发的肿瘤的发生。第二阶段将 进一步开发和验证生物测定，包括：1)表征 参数，如菌株、性别和载体，2)测定 她适合化验的致癌物的化学类别 (敏感度)，3)结构分析的使用的确定- 活动关系，4)区分能力的确定 肿瘤启动子和启动子，以及5)适合性演示 用于筛选化学预防活性物质的检测方法。一次 在15年开发并验证了促进肝脏启动的生物测定 日龄的小鼠肝脏将提供一个非常有用的商业测试系统 评估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.