Vang O, Wallin H, Autrup H
Laboratory of Environmental Carcinogenesis, Fibiger Institute, Danish Cancer Society, Copenhagen.
Arch Toxicol. 1995;69(6):415-20. doi: 10.1007/s002040050193.
Inhibition of gap junctional intercellular communication (GJIC) is a predictive short term test for tumor promoting activity. A new metabolic cooperation assay has been developed, which takes the cytochrome P-450 metabolism into account. In this assay the inhibitory activity of tobacco smoke condensates (CSC) and CSC fractions from high and low tar cigarettes was tested. CSC of both high and low tar cigarettes and fractions thereof contained tumor promoting activity. The tar yield of the cigarettes did not closely reflect the effects in the GJIC assay and the major constituent nicotine had no effect. The effect was only marginally greater in cells expressing different cytochrome P-450 enzymes, indicating that the active substances are not metabolized by these enzymes. The activities of CSC fractions were considerably lower than the activities in the unfractionated CSC. This may indicate that compounds in the CSC act strongly synergistically. Furthermore, CSC and CSC fractions synergistically inhibit GJIC with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, indicating different mechanisms of action.
抑制间隙连接细胞间通讯（GJIC）是一种预测肿瘤促进活性的短期试验。已开发出一种新的代谢合作试验，该试验考虑了细胞色素P - 450代谢。在该试验中，测试了来自高焦油和低焦油香烟的烟草烟雾浓缩物（CSC）及其馏分的抑制活性。高焦油和低焦油香烟的CSC及其馏分均具有肿瘤促进活性。香烟的焦油产率并不能紧密反映GJIC试验中的效果，且主要成分尼古丁没有作用。在表达不同细胞色素P - 450酶的细胞中，这种效果仅略大一些，表明活性物质不会被这些酶代谢。CSC馏分的活性明显低于未分级的CSC中的活性。这可能表明CSC中的化合物具有强烈的协同作用。此外，CSC和CSC馏分与肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯协同抑制GJIC，表明作用机制不同。
