IN VITRO MODELS FOR EVALUATION

长期目标是建立和验证体外系统 过氧化体增殖物(PP)的检测与研究及其危害 这些化学物质对人类健康的影响。第一阶段的具体目标是 建立和评价体外系统的可靠性，包括(1) 大鼠原代肝细胞培养，(2)大鼠肝切片培养，(3)人 肝细胞和/或切片培养。 这些体外系统将使用已知的化学物质来评估， PP和其他不引起PP的化学品，以及特定的指标 将测量PP响应。这些指标包括(1)更改 细胞内β-氧化与过氧化氢酶活性的比率，(2)DNA增加 合成；(3)细胞形态改变。这些研究的结果 应提供有关可靠性、准确性和敏感性的信息 这些检测和研究PP的机制的系统。在第二阶段 将在啮齿动物和动物身上研究各种PP诱导化学物质 人体体外系统，以更好地定义这些化学物质对 人类健康。体外系统在商业上的可用性 评估PP将使希望评估 其产品的PP诱发潜力和健康危害。

The long term objective is to establish and validate in vitro systems for detecting and studying peroxisomal proliferators (PP), and to the hazard of these chemicals to human health. The specific aims of Phase I are to establish and evaluate the reliability of in vitro systems including (1) rat primary hepatocyte culture, (2) rat liver slice culture, and (3) human hepatocyte and/or slice culture. These in vitro systems will be evaluated using chemicals known to induce PP and other chemicals which do not induce PP, and specific indicators of the PP response will be measured. These indicators include (1) altered ratios of intracellular beta-oxidation:catalase activity, (2) increased DNA synthesis, and (3) altered cell morphology. The results of these studies should provide information about the reliability, accuracy, and sensitivity of these systems for detecting and studying mechanisms of PP. In Phase II a wide variety of PP-inducing chemicals will be studied in both rodent and human in vitro systems to better define the hazard of these chemicals to human health. The commercial availability of an in vitro system for evaluating PP will significantly benefit companies who wish to evaluate the PP-inducing potential and health hazard of their products.