AN EVALUATION OF THE UTILITY OF 4 INVITRO SHORT-TERM TESTS FOR PREDICTING THE CYTO-TOXICITY OF INDIVIDUAL COMPOUNDS DERIVED FROM TOBACCO-SMOKE
AN EVALUATION OF THE UTILITY OF 4 INVITRO SHORT-TERM TESTS FOR PREDICTING THE CYTO-TOXICITY OF INDIVIDUAL COMPOUNDS DERIVED FROM TOBACCO-SMOKE
复制标题
DOI：
10.1007/bf00125573
复制
发表时间：
1984-01-01
影响因子：
6.1
通讯作者：
PETTERSSON, B
中科院分区：
文献类型：
--
作者：
CURVALL, M;ENZELL, CR;PETTERSSON, B
已经对早先获得的结果进行了评价，现在补充了305种化合物在四个体外试验中的活性信息。根据这些化合物对细胞增殖、氧化代谢、纤毛活动和膜通透性的影响，比较了它们的生物学数据，以阐明系统间的异同，并根据平均活性参数评价了结构-活性和功能-活性关系。8个N-杂环化合物、7个醇类和5个烃类。中等和低平均活性组分别包括105和131个成员，两者都包括所检查的所有功能的代表。使用45个描述符对305种化合物进行描述，并将这些化合物及其任何组合与平均活性进行计算机辅助匹配，结果显示毒性最大的单一描述符组是萜类化合物，其次是吲哚和萘，毒性最大的两个描述符组是α，β-不饱和羰基化合物，其次是正烷基醇，醛和酸。使用高-中-低标度，表明所有四个系统对35%的化合物给出相同的结果，三个系统对41%至48%的化合物给出相同的结果，两个系统对53%至64%的化合物给出相同的结果。在所有化合物中，16%的化合物在一个系统中表现出高活性，在其他三个系统中表现出低活性，反之亦然。近一半的这些差异是由膜渗透性系统显示分歧的结果，而没有一个是与棕色脂肪细胞系统。发现最后一个测试系统最能代表从四个系统中获得的平均活性，并且如果将测试次数从四个减少到一个，则选择最后一个测试系统。
An evaluation of results obtained earlier and now complemented to provide information on the activity of 305 compounds in fourin vitrotests has been undertaken. Biological data based on the effects of these compounds on cell multiplication, oxidative metabolism, ciliary activity and membrane permeability are compared with a view to clarifying intersystem similarities and differences and, on the basis of a mean activity parameter, evaluating structure-activity and functionality-activity relationships.High mean activity is observed for 59 compounds, of which 18 are phenols, 14 aldehydes, 8 N-heterocyclics, 7 alcohols and 5 hydrocarbons. The medium and low mean activity groups comprise 105 and 131 members, respectively, and both include representatives of all functionalities examined. Delineation of the 305 compounds using 45 descriptors, and computer-assisted matching of these and any combination of them against the mean activity showed the most toxic single descriptor group to be terpenoids followed by indoles and naphthalenes, and the most toxic two-descriptor group to be α, β-unsaturated carbonyls followed by n-alkyl alcohols, aldehydes and acids.Examination of intersystem similarities and differences, using a high-medium-low scale, shows that all four systems give the same result for 35 percent of the compounds, three systems for 41 to 48 percent of the compounds, and two systems for 53 to 64 percent of the compounds. Of all compounds, 16 percent exhibit a high activity in one system and a low activity in the other three, or vice versa. Nearly, half od these discrepancies are caused by the membrane permeability system showing diverging results, while none of them are related to the brown fat cell system. The last test system is found to best represent the mean activity obtained from the four systems and the one of choice if reducing the number of tests from four to one.