Richards T C
J Natl Cancer Inst. 1981 May;66(5):907-12.
The induction of adenocarcinomas in distal colons of noninbred female Swiss Webster white mice by 1,2-dimethylhydrazine (DMH) is preceded by the development of hyperplasia of mucosal glands, which includes absolute increases in both the total number of cells and labeled cells per crypt. This experiment was designed to determine if these changes are reversible. Groups of noninbred female Swiss Webster white mice were given weekly injections of DMH, 20 mg/kg body weight, for 1--20 weeks and killed 1--52 weeks after treatment. Animals were pulsed with tritiated thymidine ([3H]dTHd) for 1 hour and autoradiographs were made of sections of distal colon. The total number of cells per crypt and number of [3H]dThd-labeled cells per crypt were significantly elevated in animals killed 1 week after termination of treatment. With increasingly longer periods of recovery, base-line values were reached rapidly in animals given one or two treatments; however, reduction in cells was slower and less complete in animals given eight or more treatments. The latency before tumors developed was inversely related to the number of treatments. Animals that received 20 treatments developed more tumors per tumor-bearing animal than did animals given fewer treatments but allowed by survive for long periods. The findings indicate that once induced changes in the mucosa progress to a threshold level, mucosal glands are irreversibly enlarged and the development of tumors is irrevocable.
在非近交系雌性瑞士韦伯斯特小白鼠的远端结肠中，1,2 - 二甲基肼（DMH）诱导腺癌之前，黏膜腺体会出现增生，这包括每个隐窝中细胞总数和标记细胞数的绝对增加。本实验旨在确定这些变化是否可逆。将非近交系雌性瑞士韦伯斯特小白鼠分组，每周注射20mg/kg体重的DMH，持续1 - 20周，并在治疗后1 - 52周处死。给动物注射氚标记胸腺嘧啶核苷（[³H]dTHd）1小时，然后制作远端结肠切片的放射自显影片。在治疗终止后1周处死的动物中，每个隐窝的细胞总数和每个隐窝中[³H]dThd标记的细胞数显著升高。随着恢复时间越来越长，接受一两次治疗的动物能迅速达到基线值；然而，接受八次或更多次治疗的动物细胞减少得更慢且更不完全。肿瘤发生前的潜伏期与治疗次数呈负相关。接受20次治疗的动物比接受较少治疗但存活时间长的动物，每个荷瘤动物发生的肿瘤更多。这些发现表明，一旦黏膜诱导的变化进展到阈值水平，黏膜腺体就会不可逆地增大，肿瘤的发生也不可逆转。
