Ashby J, Mohammed R, Lefevre P A, Bandara L
ICI Central Toxicology Laboratory, Macclesfield Cheshire, UK.
Environ Mol Mutagen. 1989;14(4):221-8. doi: 10.1002/em.2850140403.
Quinoline is a specific and potent carcinogen to the rat and mouse liver. Studies are described here in which it was evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the rat liver in vivo. Although some individual animals showed indications of a marginal response the absence of clear group positive responses and the lack of an obvious dose relationship precluded the classification of quinoline as positive. The analogous NTP non-carcinogen 8-hydroxyquinoline was shown also to be devoid of UDS activity. Quinoline did, however, induce a potent mitogenic response in the rat liver between 24 and 48 hr after oral dosing of 200-500 mg/kg. Under similar conditions of test, 8-hydroxyquinoline was essentially inactive. These data represent a further instance in which mitogenicity in the liver appears to correlate better with carcinogenicity than does genotoxicity; but it may not be that simple, as discussed in the text. A single dose of quinoline was shown to act as a replacement for surgical partial hepatectomy in the liver micronucleus assay described by Tates, consistent with its potent mitogenicity.
喹啉是一种对大鼠和小鼠肝脏具有特异性和强效性的致癌物。本文描述了一些研究,评估了喹啉在大鼠肝脏中引发非程序性DNA合成(UDS)的能力。尽管一些个体动物显示出轻微反应的迹象,但缺乏明确的群体阳性反应以及明显的剂量关系,使得喹啉无法被归类为阳性。类似的NTP非致癌物8 - 羟基喹啉也被证明没有UDS活性。然而,在口服200 - 500 mg/kg剂量后24至48小时内,喹啉确实在大鼠肝脏中诱导了强烈的促有丝分裂反应。在类似的测试条件下,8 - 羟基喹啉基本无活性。这些数据代表了另一个实例,即肝脏中的促有丝分裂活性似乎比遗传毒性与致癌性的相关性更好;但正如文中所讨论的,情况可能并非那么简单。在Tates描述的肝脏微核试验中,单剂量的喹啉被证明可替代手术部分肝切除术,这与其强大的促有丝分裂活性一致。