Ito N, Imaida K, Tsuda H, Shibata M, Aoki T, de Camargo J L, Fukushima S
First Department of Pathology, Nagoya City University Medical School.
Jpn J Cancer Res. 1988 Apr;79(4):413-7. doi: 10.1111/j.1349-7006.1988.tb01606.x.
Two wide-spectrum initiation models were investigated in F344 male rats. Model I: After sequential treatment with diethylnitrosamine (DEN), N-methylnitrosourea (MNU) and dihydroxy-di-N-propylnitrosamine (DHPN), animals were given phenobarbital (PB) or N,N-dibutylnitrosamine (DBN) as a test compound for 14 weeks and sacrificed at week 18. Model II: Animals were treated with DHPN, followed by N-ethyl-N-hydroxyethylnitrosamine (EHEN), and then 3,2'-dimethyl-4-aminobiphenyl (DMAB) as initiators and were subsequently given 3-methylcholanthrene (MCA) or PB as a test compound for 11 weeks. Animals were sacrificed 16 weeks after the commencement. In both models, assessment of lesion yield revealed significant enhancement of carcinogenesis by the test compounds in their respective target organs. Since, in many cases, treatment with PB, DBN and MCA subsequent to the combined initiation procedures brought about a marked increase in lesion development, far greater than a simple sum of the yields given by initiators and test compounds alone, the presently described approach appears promising for development of medium-term bioassay systems for detection of environmental carcinogens.
在F344雄性大鼠中研究了两种广谱启动模型。模型I：在用二乙基亚硝胺（DEN）、N-甲基亚硝基脲（MNU）和二羟基二-N-丙基亚硝胺（DHPN）序贯处理后，给予动物苯巴比妥（PB）或N，N-二丁基亚硝胺（DBN）作为受试化合物，持续14周，并在第18周处死。模型II：动物先用DHPN处理，接着用N-乙基-N-羟乙基亚硝胺（EHEN）处理，然后用3，2'-二甲基-4-氨基联苯（DMAB）作为启动剂，随后给予3-甲基胆蒽（MCA）或PB作为受试化合物，持续11周。在开始处理16周后处死动物。在这两种模型中，对损伤发生率的评估显示，受试化合物在其各自的靶器官中显著增强了致癌作用。由于在许多情况下，在联合启动程序后用PB、DBN和MCA处理会使损伤发展显著增加，远远大于单独启动剂和受试化合物产生的发生率之和，因此目前描述的方法对于开发用于检测环境致癌物的中期生物测定系统似乎很有前景。
