Caderni G, Bollito E, Tessitore L
Dipartimento di Farmacologia, Università degli Studi di Firenze, Italy.
Nutr Cancer. 1999;35(2):137-42. doi: 10.1207/S15327914NC352_7.
We reported previously that fasting-refeeding enhanced the growth of preneoplastic lesions in the colon of rats induced by 20 mg/kg of azoxymethane (AOM). Here we studied whether fasting-refeeding could also affect 1) the induction of colon cancer by the same dose of AOM and 2) the induction of foci by lower doses of AOM that do not induce foci in fully fed rats. Fully fed and fasted-refed rats were given AOM by single subcutaneous injection, and the development of foci or tumors was evaluated three months or one year later. The results of the long-term carcinogenesis experiments showed that the total incidence of tumors was increased in the fasted-refed rats. Moreover, although fully fed rats developed foci only when injected with 7.5, 10, or 20 mg/kg of the carcinogen, a significant number of foci were also induced by 5 mg/kg in fasted-refed rats. The crypt multiplicity of foci was also higher when rats were exposed to fasting-refeeding, even when the number of foci was unchanged. These data suggest that growth perturbations induced by fasting-refeeding lead to the development of preneoplastic lesions with doses of AOM too low to trigger foci in fully fed rats and produce enhanced sensitivity to the development of intestinal tumors.
我们之前报道过，禁食-再喂食可促进20mg/kg氧化偶氮甲烷（AOM）诱导的大鼠结肠肿瘤前病变的生长。在此，我们研究了禁食-再喂食是否也会影响：1）相同剂量AOM诱导结肠癌的情况；2）较低剂量AOM（该剂量在正常喂食大鼠中不会诱导病灶形成）诱导病灶的情况。对正常喂食和禁食-再喂食的大鼠进行单次皮下注射AOM，并在3个月或1年后评估病灶或肿瘤的发生情况。长期致癌实验结果表明，禁食-再喂食的大鼠肿瘤总发生率增加。此外，尽管正常喂食的大鼠仅在注射7.5、10或20mg/kg致癌物时才会形成病灶，但禁食-再喂食的大鼠在注射5mg/kg时也会诱导出大量病灶。即使病灶数量不变，当大鼠经历禁食-再喂食时，病灶的隐窝多倍性也更高。这些数据表明，禁食-再喂食引起的生长紊乱会导致肿瘤前病变的发生，这些病变是由剂量过低的AOM诱导形成的，而该剂量在正常喂食大鼠中不足以触发病灶形成，并且会增强对肠道肿瘤发生的敏感性。
