Wargovich M J, Medline A, Bruce W R
J Natl Cancer Inst. 1983 Jul;71(1):125-31.
After administration of the intestinal carcinogen 1,2-dimethylhydrazine (DMH), C57BL/6J and CF1 mice were observed for early precursor lesions to large bowel cancer. Among the initial events seen following DMH treatment, an abrupt reduction in colonic DNA synthesis was the earliest lesion detectable. The frequency of aberrant colonic nuclei rose shortly after DMH treatment, reaching a maximum value 24 hours later and remaining elevated for 3 days following the exposure. Mucin changes, detected histochemically, and cell kinetic alterations in crypt proliferation rates were observed much later and were a constant feature for both strains following 4 weekly treatments with DMH, while carcinomas appeared in all animals 32 weeks after the start of DMH treatment. The quantitative comparison of these histopathologic observations for the early detection of colon cancer suggests that the induction of colonic nuclear aberrations in the mucosa of the large bowel might provide a sensitive and rapid indication of genotoxicity to this organ and thus might provide the basis for a screening methodology for colon carcinogens.
给C57BL/6J和CF1小鼠注射肠道致癌物1,2 - 二甲基肼（DMH）后，观察其是否出现大肠癌的早期前驱病变。在DMH处理后最初观察到的事件中，结肠DNA合成的突然减少是最早可检测到的病变。DMH处理后不久，异常结肠细胞核的频率升高，24小时后达到最大值，并在暴露后持续升高3天。通过组织化学检测到的黏液变化以及隐窝增殖率的细胞动力学改变在很久之后才观察到，并且在用DMH每周处理4次后，这两种品系的小鼠都持续出现这些变化，而在DMH处理开始32周后，所有动物都出现了癌。对这些组织病理学观察结果进行定量比较以早期检测结肠癌，结果表明大肠黏膜中结肠细胞核畸变的诱导可能为该器官的遗传毒性提供敏感且快速的指标，从而可能为结肠癌致癌物的筛选方法提供依据。
