Lewis D F, Ioannides C, Parke D V
Department of Biochemistry, University of Surrey, Guildford, UK.
Mutagenesis. 1990 Sep;5(5):433-5. doi: 10.1093/mutage/5.5.433.
The computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) procedure has been used to determine the molecular conformation and electronic structure of a series of 40 chemicals (out of a total of 44). The procedure can evaluate whether they interact with the active site of cytochrome P450 I or to the binding site of the Ah receptor, and hence to manifest carcinogenicity/toxicity. This is in response to the recent publication by Tennant et al. and their invitation to participate in a prospective identification of potential mutagenicity/carcinogenicity of these 44 chemicals. Correlation of COMPACT with potential genotoxicity was 25/40 (63%); COMPACT also predicted toxicity/carcinogenicity in 10 chemicals (25%) considered to be potentially non-genotoxic (naphthalene, promethazine, resorcinol, p-nitrophenol, tricresyl phosphate, bis(bromoethyl) propanediol, 3,4-dihydrocoumarin, theophylline, triamterene and chloramine), and predicted the absence of toxicity in four chemicals (10%) considered to be potentially genotoxic (methyl bromide, hydrazoic acid, 2,3-dibromo-1-propanol and 1,2,3-trichloropropane).
化学毒性的计算机优化分子参数分析（COMPACT）程序已被用于确定44种化学物质中40种化学物质的分子构象和电子结构。该程序可以评估它们是否与细胞色素P450 I的活性位点相互作用或与芳烃受体的结合位点相互作用，从而表现出致癌性/毒性。这是对Tennant等人最近发表的文章以及他们邀请参与对这44种化学物质潜在诱变性/致癌性进行前瞻性鉴定的回应。COMPACT与潜在遗传毒性的相关性为25/40（63%）；COMPACT还预测了10种被认为可能无遗传毒性的化学物质（萘、异丙嗪、间苯二酚、对硝基苯酚、磷酸三甲苯酯、双（溴乙基）丙二醇、3,4-二氢香豆素、茶碱、氨苯蝶啶和氯胺）的毒性/致癌性，并预测了4种被认为可能有遗传毒性的化学物质（甲基溴、叠氮酸、2,3-二溴-1-丙醇和1,2,3-三氯丙烷）无毒性。
