Ashby J, Lefevre P A, Elcombe C R
ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Mutagenesis. 1990 Sep;5(5):515-8. doi: 10.1093/mutage/5.5.515.
The rodent carcinogen C12-chlorinated paraffin (C12-CP) has been evaluated for unscheduled DNA synthesis (UDS) activity in the rat liver in vivo. Evidence of cell proliferation was also assessed by measuring cells undergoing semi-conservative DNA activity (S phase). No evidence of UDS was observed at doses up to 2 g/kg at either 2 or 12 h after dosing. Concomitant positive UDS responses were observed for the liver genotoxins N-nitrosodimethylamine, 4-aminobiphenyl, methyl methanesulphonate, 2-acetylaminofluorene, benzidine and 6-dimethylaminophenylazobenzthiazole. A strong positive response was observed in the cell proliferation assay for the test agent and the positive control agents quinoline and 4-acetylaminofluorene. These observations are discussed within the context of the rodent carcinogenicity reported for the same sample of C12-CPs as studied by the US National Toxicology Program.
已对啮齿动物致癌物C12 - 氯化石蜡(C12 - CP)在大鼠肝脏中的体内非程序性DNA合成(UDS)活性进行了评估。还通过测量经历半保留DNA活性(S期)的细胞来评估细胞增殖的证据。给药后2小时或12小时,在剂量高达2 g/kg时均未观察到UDS的证据。同时观察到肝脏基因毒素N - 亚硝基二甲胺、4 - 氨基联苯、甲磺酸甲酯、2 - 乙酰氨基芴、联苯胺和6 - 二甲基氨基苯基偶氮苯并噻唑的UDS阳性反应。在细胞增殖试验中,测试剂以及阳性对照剂喹啉和4 - 乙酰氨基芴均观察到强烈的阳性反应。在美国国家毒理学计划研究的同一批C12 - CP样品的啮齿动物致癌性背景下讨论了这些观察结果。