The effect of variation in carcinogenic dosage on the induction of tumours in the dorsal and vulval skin of female rats.

The response to 5, 10, 20 or 40 weekly paintings with DMBA of the dorsal and vulval skin in intact and castrate rats is compared. Squamous and basal celled tumours appear faster in the dorsal than the vulval region with 5, 10, or 20 paintings, but at the same rate with 40 doses. The rate of induction of epithelial tumours is optimal with 20 applications dorsally, but increases with dose at the vulva. Progression of malignancy of squamous celled tumours is greater and faster in the dorsal than in the vulval region. For basal celled neoplasms of the vulva there is a peak value in malignant conversion at 20 doses, but otherwise there is no consistent difference in the pattern at the two sites. Castration reduces the incidence of basal celled tumours of the vulva in rats painted weekly for life, but does not affect the incidence of epithelial tumours of the skin. Sarcomas occur in 29% of rats in the dorsal region, but in only 0·4% at the vulva. Sarcomatous changes in the stroma of epitheliomas are also more frequent in the dorsal skin. Local factors rather than variation in individual sensitivity account for the differences with region in the carcinogenic response as shown by their persistence in rats treated simultaneously at both sites.