Kunze E, Schauer A, Schatt S
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1976;87(2):139-60. doi: 10.1007/BF00284372.
The histogenesis of papillary and nonpapillary transitional cell carcinomas were studied morphologically and autoradiographically in 177 female Wistar rats after oral application of N-butyl-N-(4-hydroxybutyl)-nitrosamine with varying exposure and induction times. By far the largest proportion of carcinomas developed by a malignant transformation of preexisting papillomas or their precursors, the papillary hyperplasias. The transition into a focally malignant growth did not take place abruptly, but occurred stepwise through different successive stages of transformation, each having its own distinct morphological character. The first stage consisted of a focal, sharpely defined cellular atypia. In a further stage carcinomata in situ developed out of the atypical foci and progressed finally in a last stage of transformation into a circumscript infiltrative growth. The successive development of each stage occurred independent of any further carcinogen application after transformation was initiated at the molecular level. The number of papillomas with transformation stages increased with a lengthening of the exposure and induction time. 74.4% of all the registered papillomas had been transformed. Consequently papillomas must be considered potentially highly malignant. The 3H-TdR index was 4.2 times higher in atypical urothelial areas (7.6%) and 7.5 times higher in carcinomata in situ (14.3%) than in the surrounding papillomatous structures which appeared light microscopically benign. The latter demonstrated a rather constant 3H-TdR index, whether they bordered on atypical foci (1.8%) or carcinomata in situ (1.9%). The length of exposure and induction time exercised no significant influence on the degree of proliferative activity. The development of transitional cell carcinomas from a primary carcinoma in situ (intraurothelial carcinoma) played a much less significant role.
对177只雌性Wistar大鼠口服不同暴露时间和诱导时间的N-丁基-N-(4-羟丁基)-亚硝胺后，从形态学和放射自显影方面研究了乳头状和非乳头状移行细胞癌的组织发生。到目前为止，绝大多数癌是由先前存在的乳头状瘤或其前体即乳头状增生的恶性转化形成的。向局灶性恶性生长的转变并非突然发生，而是通过不同的连续转化阶段逐步进行的，每个阶段都有其独特的形态特征。第一阶段表现为局灶性、界限清楚的细胞异型性。在进一步的阶段，原位癌从非典型病灶发展而来，并最终在转化的最后阶段发展为局限性浸润性生长。在分子水平引发转化后，每个阶段的连续发展独立于任何进一步的致癌物应用。随着暴露和诱导时间的延长，具有转化阶段的乳头状瘤数量增加。所有登记的乳头状瘤中有74.4%发生了转化。因此，乳头状瘤必须被认为具有潜在的高度恶性。非典型尿路上皮区域的3H-TdR指数比光镜下看似良性的周围乳头状结构高4.2倍（7.6%），原位癌的3H-TdR指数比周围乳头状结构高7.5倍（14.3%）。后者的3H-TdR指数相当恒定，无论它们与非典型病灶（1.8%）还是原位癌（1.9%）相邻。暴露和诱导时间的长短对增殖活性程度没有显著影响。原位癌（尿路上皮内癌）发展为移行细胞癌所起的作用要小得多。
