Lewis D F, Ioannides C, Parke D V
Molecular Toxicology Group School of Biological Sciences, University of Surrey, Guildford, UK.
Environ Health Perspect. 1995 Feb;103(2):178-84. doi: 10.1289/ehp.95103178.
The carcinogenic potentials of 40 National Toxicology Program chemicals previously predicted by Computer Optimised Molecular Parametric Analysis for Chemical Toxicity (COMPACT), based on the identification of potential substrates of cytochromes P4501A and 2E (CYP1A and CYP2E), have been compared with new rodent carcinogenicity results. The COMPACT predictions have also been compared with published Ames mutagenicity data and with our own Hazardexpert predictions for carcinogenicity. Concordance evaluations between rodent carcinogenicity (1/4 segments positive) and predictions by COMPACT or Hazardexpert were 64% for COMPACT (CYP1A only), 72% for COMPACT (CYP1A plus CYP2E), 70% for Hazardexpert alone, and 86% for COMPACT (CYP1A plus CYP2E) plus Hazardexpert. Sensitivities of the predictions were for COMPACT, 75%; Hazardexpert, 60%; and Ames, 54%. Positive predictivities were for COMPACT, 75%; Hazardexpert, 78%; and Ames 81%. Negative predictivites were for COMPACT, 62%; Hazardexpert, 52%; and Ames, 42%.
基于对细胞色素P4501A和2E（CYP1A和CYP2E）潜在底物的识别，通过计算机优化分子参数化学毒性分析（COMPACT）先前预测的40种美国国家毒理学计划化学品的致癌潜力，已与新的啮齿动物致癌性结果进行了比较。COMPACT预测还与已发表的艾姆斯致突变性数据以及我们自己的Hazardexpert致癌性预测进行了比较。啮齿动物致癌性（1/4段呈阳性）与COMPACT或Hazardexpert预测之间的一致性评估结果为：仅COMPACT（CYP1A）为64%，COMPACT（CYP1A加CYP2E）为72%，仅Hazardexpert为70%，COMPACT（CYP1A加CYP2E）加Hazardexpert为86%。预测的敏感性分别为：COMPACT为75%；Hazardexpert为60%；艾姆斯试验为54%。阳性预测值分别为：COMPACT为75%；Hazardexpert为78%；艾姆斯试验为81%。阴性预测值分别为：COMPACT为62%；Hazardexpert为52%；艾姆斯试验为42%。
