Moore M A, Mayer D, Bannasch P
Carcinogenesis. 1982;3(12):1429-36. doi: 10.1093/carcin/3.12.1429.
Different doses of N-nitrosomorpholine (NNM) (80, 120, 160, 200 mg/l drinking water) were administered for various periods of time (1, 4, 7, 14, 20 weeks) to male Sprague-Dawley rats in order to investigate the dose dependence and sequential appearance of preneoplastic and neoplastic lesions in the liver. With all dose levels studied a sequence was established leading from clear cell and acidophilic cell glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas. The first appearance and frequency of the different lesions investigated proved dependent on dose of carcinogen administered. Morphometric analysis demonstrated that the rare small clear cell foci apparent after 7 weeks treatment with NNM increase in number and size with progression through the sequence to carcinomas without further administration of carcinogen. No evidence was found to suggest that pronounced focal populations were reversible upon cessation of NNM-treatment under the present experimental conditions.
为了研究肝内癌前病变和肿瘤性病变的剂量依赖性及相继出现情况，将不同剂量的N-亚硝基吗啉（NNM）（80、120、160、200毫克/升饮用水）给予雄性斯普拉格-道利大鼠，持续不同时间段（1、4、7、14、20周）。在所研究的所有剂量水平下，建立了一个序列，从透明细胞和嗜酸性细胞糖原储存灶，经混合细胞灶和肿瘤结节，发展到肝细胞癌。所研究的不同病变的首次出现及频率证明取决于所给予致癌物的剂量。形态计量分析表明，用NNM处理7周后出现的罕见小透明细胞灶，在不进一步给予致癌物的情况下，随着病变进展至癌，其数量和大小会增加。在当前实验条件下，未发现有证据表明停止NNM处理后明显的局灶性病变群是可逆的。
