Matsui I, Pegg A E
Cancer Res. 1982 Aug;42(8):2990-5.
Treatment of rats with dimethylnitrosamine (30 mg/kg) or diethylnitrosamine (200 mg/kg) produced a rapid increase in the activity of spermidine N1-acetyltransferase which peaked at values 7-fold greater than did control at 48 hr after exposure. This increase led to a small accumulation of N1-acetylspermidine in the liver but produced a more striking effect on putrescine which increased 30- to 40-fold after 2 days. Most of this increase appeared to be due to the conversion of N1-acetylspermidine into putrescine which is catalyzed by polyamine oxidase. Treatment with the nitrosamines also increased the conversion of spermine into spermidine which replaced the spermidine converted into putrescine. Spermine levels were therefore significantly depressed by treatment with these carcinogens. These results indicate that these hepatocarcinogens bring about an increase in putrescine and in the spermidine/spermine ratio in the liver not only by enhancement of ornithine decarboxylase but also by induction of the spermidine N1-acetyltransferase activity which is the rate-limiting step in the acetylase-oxidase pathway for interconversion of the polyamines.
用二甲基亚硝胺（30毫克/千克）或二乙基亚硝胺（200毫克/千克）处理大鼠后，亚精胺N1 - 乙酰转移酶的活性迅速增加，在接触后48小时达到峰值，比对照组高7倍。这种增加导致肝脏中N1 - 乙酰亚精胺有少量积累，但对腐胺产生了更显著的影响，2天后腐胺增加了30至40倍。这种增加大部分似乎是由于多胺氧化酶催化N1 - 乙酰亚精胺转化为腐胺。用亚硝胺处理也增加了精胺向亚精胺的转化，从而取代了转化为腐胺的亚精胺。因此，用这些致癌物处理后精胺水平显著降低。这些结果表明，这些肝癌致癌物不仅通过增强鸟氨酸脱羧酶，而且通过诱导亚精胺N1 - 乙酰转移酶活性，使肝脏中的腐胺和亚精胺/精胺比值增加，而该酶活性是多胺相互转化的乙酰酶 - 氧化酶途径中的限速步骤。
