Yarita T, Nettesheim P
Int J Cancer. 1978 Sep 15;22(3):298-303. doi: 10.1002/ijc.2910220313.
Tracheal tumors were induced by repeated intratracheal exposures to the carcinogen N-nitroso-N-methylurea (NMU), using a catheter system previously described. Carcinogen concentrations of 0.25, 0.50 and 1.0% were employed in 20 or 30 twice-weekly exposures. Most of the tumors developed in the mid-portion of the tracheas. Virtually all tumors developed after the end of the 10- to 15-week exposure period. Tumor incidence ranged from 20-94% with mean tumor induction times of 13-46 weeks, depending on NMU concentration and frequency of exposure (i.e., dose). At lower doses, mostly non-invasive tumors were induced; at higher doses, mostly invasive carcinomas of various histological types (epidermoid, adeno-, epidermoid-adeno, and anaplastic large- and small-cell carcinomas) were induced. Adenocarcinomas were most frequent at low NMU concentrations. The possible mechanisms of the carcinogen dose effects are discussed.
使用先前描述的导管系统，通过反复经气管暴露于致癌物N-亚硝基-N-甲基脲（NMU）来诱发气管肿瘤。每周两次，分别进行20次或30次暴露，使用的致癌物浓度分别为0.25%、0.50%和1.0%。大多数肿瘤发生在气管中部。几乎所有肿瘤都在10至15周的暴露期结束后出现。根据NMU浓度和暴露频率（即剂量），肿瘤发生率在20%至94%之间，平均肿瘤诱发时间为13至46周。在较低剂量下，主要诱发非侵袭性肿瘤；在较高剂量下，主要诱发各种组织学类型的侵袭性癌（表皮样癌、腺癌、表皮样腺癌以及间变性大细胞和小细胞癌）。在低NMU浓度下，腺癌最为常见。本文讨论了致癌物剂量效应的可能机制。
