Pereira M A, Khoury M M, Glauert H P, Davis R A
Environmental Health Research and Testing, Inc., Cincinnati, OH 45245.
Cancer Lett. 1991 Apr;57(1):37-44. doi: 10.1016/0304-3835(91)90060-u.
Five alkyl carbamates, methyl, ethyl, propyl, hydroxypropyl and ethylhexyl, were tested for initiating and promoting activity in rat liver. The test for initiating activity consisted of administering the carbamate by gavage to male Sprague--Dawley rats at either 6 or 18 h after a 2/3 partial hepatectomy. One week later, the rats received 500 ppm sodium phenobarbital in their drinking water until killed 10 weeks later. None of the carbamates at 1/5 the LD50 induced gamma-glutamyltranspeptidase (GGT)-positive foci, indicating the lack of initiating activity. The tumor promoting activity test consisted of initiation with 80 mmol/kg diethylnitrosamine administered 18 h after a partial hepatectomy. One week later, the rats received one of the the carbamates at either 1/10 or 1/20 the LD50 5 days per week until sacrificed 10 weeks later. The alkyl carbamates increased the volume of the foci, the percent of the liver occupied by the foci, the number of foci/cm3 (except ethylhexyl carbamate), and the number of foci/liver (except ethylhexyl carbamate). These results suggest that the alkyl carbamates are tumor promoters and not tumor initiators in rat liver.
对甲基、乙基、丙基、羟丙基和乙基己基这五种氨基甲酸酯进行了大鼠肝脏启动和促癌活性测试。启动活性测试包括在2/3部分肝切除术后6小时或18小时,通过灌胃给雄性斯普拉格-道利大鼠施用氨基甲酸酯。一周后,大鼠在饮用水中摄入500 ppm苯巴比妥钠,直至10周后处死。1/5半数致死剂量(LD50)的任何一种氨基甲酸酯均未诱导γ-谷氨酰转肽酶(GGT)阳性灶,表明缺乏启动活性。促癌活性测试包括在部分肝切除术后18小时,用80 mmol/kg二乙基亚硝胺进行启动。一周后,大鼠每周5天接受1/10或1/20 LD50的一种氨基甲酸酯,直至10周后处死。氨基甲酸酯增加了病灶的体积、病灶占据肝脏的百分比、每立方厘米病灶的数量(乙基己基氨基甲酸酯除外)以及每个肝脏病灶的数量(乙基己基氨基甲酸酯除外)。这些结果表明,氨基甲酸酯在大鼠肝脏中是促癌剂而非启动剂。