Tessitore L
Dipartimento di Scienze Cliniche e Biologiche, Ospedale S. Luigi Gonzaga, Orbassano, TO, Italy.
Nutr Cancer. 1998;32(1):49-54. doi: 10.1080/01635589809514716.
We reported elsewhere that diethylnitrosamine (DENA) at 20 mg/kg triggered the development of liver foci in fasted-refed rats. Here we investigate whether liver cancer is induced by this dose of DENA when administered to previously fasted-refed animals. Fischer 344 rats, fasted for four days, were given 20 mg/kg DENA after one day of refeeding; regularly fed animals receiving 20 or 200 mg/kg DENA were used as negative and positive controls, respectively. The rats were selected by the promoting regimen of Solt and Farber. Focal proliferative lesions, nodules, and carcinomas developed in the liver of fasted-refed rats given 20 mg/kg DENA and, as expected, in the liver of positive controls. Neither preneoplastic nor neoplastic lesions were found in the negative controls. The liver initiation in fasted-refed rats was steadily irreversible, as reflected by the growth of foci, even when the promoting regimen was postponed. The data show that fasting-refeeding can substitute for any compensatory proliferative stimulus to make the subnecrogenic dose of DENA able to initiate hepatocytes, eventually leading to the development of liver cancer.
我们在其他地方报道过，20mg/kg的二乙基亚硝胺（DENA）可在禁食-再喂食的大鼠中引发肝灶的形成。在此，我们研究将此剂量的DENA给予先前禁食-再喂食的动物时是否会诱发肝癌。禁食四天的Fischer 344大鼠在再喂食一天后给予20mg/kg DENA；分别将接受20mg/kg或200mg/kg DENA的正常喂食动物作为阴性和阳性对照。大鼠通过Solt和Farber的促癌方案进行筛选。给予20mg/kg DENA的禁食-再喂食大鼠的肝脏以及如预期的阳性对照大鼠的肝脏中出现了局灶性增殖性病变、结节和癌。阴性对照中未发现癌前病变或肿瘤性病变。即使推迟促癌方案，禁食-再喂食大鼠肝脏中的起始过程也是稳定且不可逆的，这可通过病灶的生长反映出来。数据表明，禁食-再喂食可替代任何代偿性增殖刺激，使亚致死剂量的DENA能够启动肝细胞，最终导致肝癌的发生。
