Hermanek P J, Giedl J
Pathol Res Pract. 1984 Jul;178(6):548-54. doi: 10.1016/s0344-0338(84)80087-4.
There is general agreement today that most colorectal carcinomas develop from adenomas via the so-called adenoma-carcinoma-sequence. There has however in addition been a discussion regarding the possibility of carcinomas arising "de-novo". The aim of the present study was to find out alterations preceding carcinomas in animal experiment and to demonstrate possible similarities to man. For colonic tumor induction in 40 male Sprague-Dawley rats the local acting nitrosamine-derivative acetoxymethyl-methylnitrosamine was instilled intrarectally once a week for 6 weeks in a dosage of 2 mg/kg bodyweight. 14 weeks after the end of the tumor induction those 28 animals, that had developed endoscopically recognizable tumors, were randomized into two groups. The animals from group I were sacrificed 3 weeks, the animals from group II 20 weeks later, that is 23 and 40 weeks after the start of the experiment. At histopathologic examination an increase of the number of tumors per animal and a doubling of the mean tumor diameter could be observed in group II. The most severe findings (adenoma, adenoma with dysplasia, carcinoma) were more pronounced in group II. "De-novo" carcinomas without residues of benign adenomas were not found. It could be demonstrated, that chemically induced colonic tumours produced in the way described, develop in a fashion quite similar to the conditions found in man via the adenoma-carcinoma-sequence.
如今人们普遍认为，大多数结直肠癌是通过所谓的腺瘤-癌序列从腺瘤发展而来的。然而，关于癌症“从头”发生的可能性也存在讨论。本研究的目的是在动物实验中找出癌症发生之前的变化，并证明与人类可能存在的相似之处。为了在40只雄性Sprague-Dawley大鼠中诱导结肠肿瘤，每周一次经直肠注入局部作用的亚硝胺衍生物乙酰氧甲基甲基亚硝胺，持续6周，剂量为2mg/kg体重。在肿瘤诱导结束14周后，将28只经内镜检查发现有肿瘤的动物随机分为两组。第一组动物在3周后处死，第二组动物在20周后处死，即实验开始后的23周和40周。在组织病理学检查中，第二组动物每只动物的肿瘤数量增加，平均肿瘤直径加倍。最严重的病变（腺瘤、发育异常的腺瘤、癌）在第二组中更为明显。未发现无良性腺瘤残留的“从头”癌。可以证明，以所述方式化学诱导产生的结肠肿瘤，其发展方式与人类通过腺瘤-癌序列所发现的情况非常相似。
