Correa E, Joshi P A, Castonguay A, Schüller H M
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Cancer Res. 1990 Jun 1;50(11):3435-8.
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen in adult laboratory rodents. Our previous studies have shown that NNK crosses the placenta in pregnant hamsters and is metabolized into DNA-methylating and clastogenic intermediates by fetal respiratory tract tissues. Based on these findings, we have tested the transplacental carcinogenicity of NNK in this species. Groups of pregnant hamsters were given s.c. injections of single or multiple doses of NNK (cumulative dose range, 50-300 mg/kg) on day 15 (last day of gestation) or on days 13, 14, and 15 of gestation. Within 1 year after treatment, up to 70% of the offspring developed tumors in various organs, including respiratory tract, nasal cavity, adrenal glands, pancreas, and liver. No tumors were found in the control hamsters treated with the vehicle (trioctanoin) alone. The overall tumor incidence was proportional to the cumulative dose. Females had a generally higher tumor incidence than males.
烟草特异性亚硝胺4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮(NNK)是成年实验啮齿动物中的一种强效致癌物。我们之前的研究表明,NNK可穿过怀孕仓鼠的胎盘,并被胎儿呼吸道组织代谢为DNA甲基化和致染色体断裂的中间体。基于这些发现,我们在该物种中测试了NNK的经胎盘致癌性。在妊娠第15天(妊娠最后一天)或妊娠第13、14和15天,给怀孕仓鼠组皮下注射单剂量或多剂量的NNK(累积剂量范围为50-300mg/kg)。治疗后1年内,高达70%的后代在包括呼吸道、鼻腔、肾上腺、胰腺和肝脏在内的各个器官中发生肿瘤。单独用载体(三辛酸甘油酯)治疗的对照仓鼠未发现肿瘤。总体肿瘤发生率与累积剂量成正比。雌性的肿瘤发生率通常高于雄性。