Prediction of rodent carcinogenesis: An evaluation of prechronic liver lesions as forecasters of liver tumors in NTP carcinogenicity studies
Prediction of rodent carcinogenesis: An evaluation of prechronic liver lesions as forecasters of liver tumors in NTP carcinogenicity studies
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DOI：
10.1080/01926230490440934
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发表时间：
2004-07-01
影响因子：
1.5
通讯作者：
Maronpot, RR
中科院分区：
文献类型：
--
作者：
Allen, DG;Pearse, G;Maronpot, RR
国家毒理学计划（NTP）开发了慢性2年生物测定法，作为预测化学品对人类致癌潜力的机制。这些研究的费用和持续时间限制了它们对少数选定化学品的使用。已经开发了许多不同的短期方法，旨在提高预测准确性和评估的化学品数量，试图成功地将其结果与致癌性（或缺乏致癌性）的证据相关联。使用NTP研究，评估了将慢性前肝病变与肝癌相关联的有效性，包括使用小鼠（83种化合物）和大鼠（87种化合物）的多项研究。这些病变包括肝细胞坏死、肝细胞肥大、肝细胞巨细胞、胆管增生和肝细胞变性，沿着肝脏重量增加。我们的研究结果表明，在2年研究中，合并这些慢性前数据点中的3个（肝细胞坏死、肝细胞肥大和肝细胞巨细胞）可以很好地预测致癌性（p < 0.05）。将肝脏重量增加作为终点纳入数据点库增加了成功预测的啮齿动物肝脏致癌物的数量（p < 0.05），但也导致预测非致癌化学品作为致癌物的数量增加。使用多个慢性前研究终点提供了补充信息，提高了识别具有致癌潜力的化学品的预测性。
The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity ( or lack of carcinogenicity). Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice ( 83 compounds) and rats (87 compounds) was assessed. These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increased liver weight. Our results indicate that pooling 3 of these prechronic data points ( hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular cytomegaly) can be very predictive of carcinogenicity in the 2-year study (p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted ( p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.