Glucksmann A, Cherry C P
Br J Cancer. 1970 Dec;24(4):769-84. doi: 10.1038/bjc.1970.92.
Medication with L-thyroxine or methylthiouracil of castrate rats painted weekly 5, 10, 20 or 40 times with DMBA does not alter the order of thresholds for carcinogenesis which increases from that for cervico-vaginal epitheliomas via squamous celled and basal celled vulval tumours to cervicovaginal sarcomas. Methylthiouracil lowers the threshold for basal celled vulval neoplasms.Sarcomas reach a peak of 25% with 20 doses of DMBA in non-medicated rats, but rise to 90% and at a faster rate in animals given either of the thyroactive drugs with further carcinogenic treatment.The optimal dose phenomenon for cervico-vaginal epitheliomas, i.e. a significant fall with continued painting from a peak reached by 5 to 20 doses of DMBA, is not affected by medication with methylthiouracil or L-thyroxine.Thyroactive compounds accelerate the formation of squamous celled vulval tumours which reach a maximum with 20 DMBA paintings; the total incidence as well as the proportion of carcinomas to papillomas falls with further treatment.Methylthiouracil promotes formation of basal celled vulval tumours at low dose levels, but inhibits it at the highest. In medicated as in non-medicated rats the induction of basal celled tumours of the vulva follows an optimum dose pattern.The optimal dose phenomenon and the effect of thyroactive compounds on the tissue-specific sensitivity to carcinogens are discussed.
每周用二甲基苯并蒽（DMBA）给去势大鼠涂抹5、10、20或40次，同时给予左旋甲状腺素或甲基硫氧嘧啶进行药物处理，并不会改变致癌阈值的顺序，该顺序从宫颈阴道上皮瘤开始，经鳞状细胞和基底细胞外阴肿瘤，再到宫颈阴道肉瘤，致癌阈值逐渐升高。甲基硫氧嘧啶降低了基底细胞外阴肿瘤的阈值。在未用药的大鼠中，给予20剂DMBA后肉瘤发生率达到峰值25%，但在给予任何一种甲状腺活性药物并进一步进行致癌处理的动物中，肉瘤发生率上升至90%，且上升速度更快。宫颈阴道上皮瘤的最佳剂量现象，即从5至20剂DMBA达到的峰值开始持续涂抹时显著下降，不受甲基硫氧嘧啶或左旋甲状腺素药物处理的影响。甲状腺活性化合物加速了鳞状细胞外阴肿瘤的形成，在涂抹20次DMBA时达到最大值；随着进一步处理，总发生率以及癌与乳头状瘤的比例均下降。甲基硫氧嘧啶在低剂量水平促进基底细胞外阴肿瘤的形成，但在高剂量时抑制其形成。在用药和未用药的大鼠中，外阴基底细胞瘤的诱导均遵循最佳剂量模式。文中讨论了最佳剂量现象以及甲状腺活性化合物对组织对致癌物特异性敏感性的影响。
