Glatt H R, Schwind H, Zajdela F, Croisy A, Jacquignon P C, Oesch F
Mutat Res. 1979 Apr;66(4):307-28. doi: 10.1016/0165-1218(79)90042-9.
43 heteropolycyclic compounds belonging to a homologous series were investigated for mutagenicity. The results are compared with carcinogenicity data obtained with the same batches of compounds under conditions identical for all of them. Mutagenicity was tested in the Ames test with Salmonella typhimurium strains TA1535, TA1537 and TA100 in the presence and absence of liver 10 000 g supernatant from rats treated with Aroclor 1254. Carcinogenicity was tested by injection of the compounds into subcutaneous tissue of XVIInc/Z mice. 18 test compounds showed carcinogenic activity, some strongly, others only weakly. Of these, 17 were detected as mutagens: one weak carcinogen did not revert the Salmonella strains. No quantitative correlation was observed between the extents of the mutagenic and the carcinogenic effects. Of the 25 substances that did not produce tumours, 13 showed mutagenicity (12 in the presence, 2 in the absence, of the liver homogenate). The mutagenic effects of these compounds were quantitatively similar to those of the compounds that produced tumours. The most sensitive strain of Salmonella typhimurium was TA100. It detected all 30 mutagens. TA98 was mutated by 25 compounds, TA1537 by 16 compounds. No mutagenic effects were seen with TA1535. Possible reasons for the high percentage of apparently "false positives" in the Ames test and the lack of a quantitative correlation between the potency of the mutagenic and carcinogenic effects are discussed. It is suggested that the complexity of the metabolism of these heterocyclic compounds may lead to critical differences in metabolism in mouse subcutaneous tissue in vivo and in liver homogenates from rats treated with Aroclor. Therefore the present study will be extended to life-long oral and intrahepatic carcinogenicity tests leading to a higher proportion of metabolism in the liver.
对属于同系物系列的43种杂环化合物进行了致突变性研究。将结果与在相同条件下对同一批化合物获得的致癌性数据进行比较。在有和没有用多氯联苯混合物1254处理的大鼠肝脏10000g上清液存在的情况下，用鼠伤寒沙门氏菌TA1535、TA1537和TA100菌株进行Ames试验来检测致突变性。通过将化合物注射到XVIInc/Z小鼠的皮下组织中来检测致癌性。18种受试化合物显示出致癌活性，有些很强，有些则较弱。其中，17种被检测为诱变剂：一种弱致癌物未使沙门氏菌菌株发生回复突变。在诱变作用和致癌作用的程度之间未观察到定量相关性。在25种未产生肿瘤的物质中，13种显示出致突变性（12种在有肝脏匀浆存在时，2种在没有肝脏匀浆时）。这些化合物的诱变作用在数量上与产生肿瘤的化合物相似。鼠伤寒沙门氏菌最敏感的菌株是TA100。它检测到了所有30种诱变剂。TA98被25种化合物诱变，TA1537被16种化合物诱变。TA1535未观察到诱变作用。讨论了Ames试验中明显“假阳性”比例高以及诱变作用和致癌作用强度之间缺乏定量相关性的可能原因。有人认为，这些杂环化合物代谢的复杂性可能导致体内小鼠皮下组织和用多氯联苯混合物处理的大鼠肝脏匀浆中的代谢存在关键差异。因此，本研究将扩展到终身口服和肝内致癌性试验，以使肝脏中的代谢比例更高。
