Topping D C, Griesemer R A, Nettesheim P
Cancer Res. 1979 Dec;39(12):4823-8.
Sequential morphological changes occurring after brief carcinogen exposures of heterotopic tracheal transplants in rats were semiquantitatively studied. Tracheas were exposed to 7,12-dimethylbenz(a)anthracene for 1, 2, or 4 weeks, during which time means of 138, 152, and 160 microgram 7,12-dimethylbenz(a)anthracene, respectively, were delivered. The first two types of exposures resulted only in generalized epithelial changes; these included hyperplasia and early metaplasia, both of which regressed rapidly, and persistent atrophic alterations. No focal epithelial lesions or tumors developed. The third type of exposure (160 microgram 7,12-dimethylbenz(a)anthracene delivered in 4 weeks) resulted in the appearance of generalized mucosal changes with long-lasting, severe inhibition of mucus production. In addition, focal metaplastic lesions reappeared at 4 to 8 months after exposure, and invasive carcinomas developed after 1 year with an incidence of 9%. Overall carcinoma incidence, including carcinoma in situ, was 15%. The studies emphasize the importance of the duration of carcinogen exposure, and they demonstrate the emergence of focal lesions when effective carcinogenic exposures are being used. The possible significance of epithelial atrophy in the pathogenesis of cancer in this experimental model is discussed.
对大鼠异位气管移植在短暂接触致癌物后发生的一系列形态学变化进行了半定量研究。将气管暴露于7,12-二甲基苯并(a)蒽中1、2或4周，在此期间分别给予138、152和160微克的7,12-二甲基苯并(a)蒽。前两种暴露类型仅导致全身性上皮变化；这些变化包括增生和早期化生，两者均迅速消退，以及持续性萎缩性改变。未出现局灶性上皮病变或肿瘤。第三种暴露类型（4周内给予160微克7,12-二甲基苯并(a)蒽）导致全身性黏膜变化的出现，伴有黏液分泌的长期严重抑制。此外，暴露后4至8个月局灶性化生病变再次出现，1年后发生浸润性癌，发病率为9%。包括原位癌在内的总体癌发病率为15%。这些研究强调了致癌物暴露持续时间的重要性，并证明了在使用有效致癌暴露时局灶性病变的出现。讨论了上皮萎缩在该实验模型癌症发病机制中的可能意义。
