Chan P C, Cohen L A, Narisawa T, Weisburger J H
Cancer Res. 1976 Jan;36(1):13-7.
The early morphological and biochemical effects of intrarectally administered 1,2-dimethylhydrazine dihydrochloride on mouse colon were studied. Using [3H]thymidine autoradiography, it was found that 1,2-dimethylhydrazine dihydrochloride, 250 mg/kg decreased the number of prelabeled DNA-synthesizing cells in the distal colon as early as 30 min after instillation. During the interval from 24 hr to 2 weeks, however, the opposite effect was seen; incorporation of [3H]thymidine increased 3- to 5-fold over controls. At lower doses (0.25 to 25 mg/kg), a similar trend was observed. Histological examination showed no dramatic changes in cell structure or in tissue architecture. No changes were seen in labeling indices in the proximal colon. In the liver, cellular alterations were seen at concentrations of 25 to 250 mg/kg, particularly in the centrolobular region. These changes were evident at 2 hr and disappeared by 4 hr. The kidney was unaffected by 1,2-dimethylhydrazine dihydrochloride at any concentration. Our results suggest that enzymes capable of activating 1,2-dimethylhydrazine dihydrochloride are located within the mucosal cells of the distal colon.
研究了经直肠给予盐酸1,2 - 二甲基肼对小鼠结肠的早期形态学和生化效应。利用[³H]胸腺嘧啶核苷放射自显影技术发现，250mg/kg的盐酸1,2 - 二甲基肼在滴注后30分钟，就使远端结肠中预先标记的DNA合成细胞数量减少。然而，在24小时至2周的时间段内，却出现了相反的效应；[³H]胸腺嘧啶核苷的掺入量比对照组增加了3至5倍。在较低剂量（0.25至25mg/kg）时，也观察到了类似的趋势。组织学检查显示细胞结构或组织结构没有明显变化。近端结肠的标记指数未见改变。在肝脏中，当浓度为从25至250mg/kg时可见细胞改变，特别是在小叶中心区域。这些变化在2小时时明显，4小时时消失。肾脏在任何浓度的盐酸1,2 - 二甲基肼作用下均未受影响。我们的结果表明，能够激活盐酸1,2 - 二甲基肼的酶位于远端结肠的黏膜细胞内。
