Cherry C P, Glucksmann A
Br J Cancer. 1971 Sep;25(3):544-64. doi: 10.1038/bjc.1971.70.
The effect of varying the numbers (4, 5, 10, 20 and 40) of weekly applications of DMBA to the dorsal skin of intact and castrate male and female rats on the induction of basal and squamous celled epitheliomas and of sarcomas has been investigated.Basal celled tumours originate mainly in hair follicles and squamous celled neoplasms in the interfollicular regions of the epidermis and differ in their progression to malignancy. Penetration of the panniculus carnosus is neither a sufficient nor necessary criterion of malignancy since growing hair follicles pass through the muscle layer and carcinomas and sarcomas which are still confined to the dermis, spread along the perineural lymphatics and metastasise to the lungs.Sex and castration do not affect carcinogenesis of epitheliomas in the dorsal skin at any dose level. Significantly more sarcomas result from 20 weekly paintings in male than in female or castrate rats.The induction period for all tumour types is shortened in sensitive individuals only by an increase from 5 to 10 weekly applications. For less sensitive animals the rate of oncogenesis is accelerated with number of administrations up to 20, but slowed down from this level by 40 paintings. The optimal dose for speed of induction of all tumour types, for maximal yield of basal celled epitheliomas and for that of sarcomas in male rats is 20 weekly applications.THE PROGRESSION TO MALIGNANCY VARIES WITH TUMOUR TYPE: it is fast for sarcomas and slow for basal celled neoplasms. Of the 336 rats at risk only 1% have fibromas or other precursor lesions, while 40% have sarcomas; animals with squamous celled papillomas account for 12%, but those with carcinomas for 66%; there are, however, 64% of rats with basal celled papillomas and only 9% with carcinomas.The optimal dose phenomenon in carcinogenesis is discussed.
研究了每周向完整及去势的雄性和雌性大鼠背部皮肤涂抹不同次数（4、5、10、20和40次）的二甲基苯蒽（DMBA）对基底细胞上皮瘤、鳞状细胞上皮瘤和肉瘤诱导的影响。基底细胞肿瘤主要起源于毛囊，鳞状细胞肿瘤起源于表皮的毛囊间区域，它们向恶性发展的过程有所不同。肉膜的穿透既不是恶性的充分标准也不是必要标准，因为生长中的毛囊会穿过肌肉层，而仍局限于真皮的癌和肉瘤会沿神经周围淋巴管扩散并转移至肺部。性别和去势在任何剂量水平下都不影响背部皮肤上皮瘤的致癌作用。雄性大鼠每周涂抹20次比雌性或去势大鼠产生的肉瘤明显更多。仅在敏感个体中，将每周涂抹次数从5次增加到10次可缩短所有肿瘤类型的诱导期。对于不太敏感的动物，致癌作用速率在给药次数增加至20次时加快，但从这个水平增加到40次涂抹时则减慢。对于所有肿瘤类型的诱导速度、雄性大鼠基底细胞上皮瘤的最大产量以及肉瘤的最大产量而言，最佳剂量是每周涂抹20次。向恶性发展的过程因肿瘤类型而异：肉瘤发展迅速，基底细胞肿瘤发展缓慢。在336只处于风险中的大鼠中，只有1%患有纤维瘤或其他前驱病变，而40%患有肉瘤；患有鳞状细胞乳头状瘤的动物占12%，但患有癌的动物占66%；然而，患有基底细胞乳头状瘤的大鼠占64%，患有癌的仅占9%。文中讨论了致癌作用中的最佳剂量现象。
