The Influence of Carcinogenic Dosage and of Sex on the Induction of Epitheliomas and Sarcomas in the Dorsal Skin of Rats

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Abstract
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.