Rabes H M, Kerler R, Wilhelm R
J Natl Cancer Inst. 1983 Jan;70(1):193-8.
Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of [14C]N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.
使用部分肝切除术后同步再生的大鼠肝脏来研究细胞周期相关的DNA碱基烷基化和肝癌发生。对近交系雄性Wistar Af/Han大鼠连续静脉输注剂量为0.5 mg/kg/小时的[14C]N-亚硝基二甲胺（DMN），持续8小时，输注时间分别为再生肝脏的G1期、羟基脲同步化的DNA合成期或G2+M期，或者对未处理的大鼠（G0期肝脏 - 致癌物剂量为1.5 mg/kg/小时）进行输注。输注结束后两小时，G0期肝脏中7-甲基鸟嘌呤的含量最高，在G1期、S期和G2+M期含量降低。连续暴露于DMN后，S期和G2+M期肝脏中的O6-甲基鸟嘌呤:7-甲基鸟嘌呤比值低于G0期和G1期肝脏，表明在DNA合成期和G2+M期O6-甲基鸟嘌呤修复增加。在G0期或S期通过连续输注DMN处理的大鼠，仅在DNA合成期暴露于致癌物后才会发生肝肿瘤。
