Carcinogenesis in the Pituitary Dwarf Mouse. The Response to Dimethylbenzanthracene Applied to the Skin

THE response to a carcinogen is determined not only by the nature and the quantity of the agent but also by genetic and epigenetic factors which influence tissue susceptibility. In mice the reaction to agents inducing lymphatic leukaemia depends on genetic constitution, endocrine status (Kaplan, Nagareda and Brown, 1954) and on the presence or absence of the thymus. In rats presence or absence of the adenohypophysis determines whether cancer of the liver will or will not develop after administration of azo dyes or of aminofluorene and related compounds. Generally it is not difficult to make a distinction between the role of genetic and of epigenetic factors in carcinogenesis, but in the case of the pituitary dwarf mouse it is less easy to differentiate between the two. Pituitary dwarfism is due to an inherited defect of the adenohypophysis and in consequence, through lack of trophic pituitary hormones, a complex hormonal deficiency is present in these animals, an epigenetic phenomenon. Although most of the secondary disorders affecting gonads, thyroids and adrenals can be rectified by substitution therapy, complete normalization of the female dwarf mouse has not bee

Investigations on the Role of Thyroxine in the Development of Hepatomas in Hypophysectomized Rats and Pituitary Dwarf Mice

IT has been shown that the susceptibility of epithelial tissues to powerful chemical carcinogens is not a constant entity determined solely by the genetic constitution but varies according to the endocrine status of the experimental animal. The importance of the endocrine status is easily demonstrated when the liver is the target organ of the carcinogen, because the difference between the response of the intact and that of the hypophysectomized (Griffin, Rinfret and Corsigilia, 1953) or thyroidectomized (Bielschowsky and Hall, 1953) rat to hepatoma inducing agents is of an order of magnitude sufficient to make statistical treatment of results superfluous. After ablation of these glands the liver is refractory to azo dyes as well as to aminofluorene and its derivatives. How this effect comes about is still problematical; neither has the role of individual hormones been elucidated, nor is it certain whether the hormonal requirements necessary for the development of liver tumours are the same for all agents (O'Neal, Hoffman, Dodge and Griffin, 1958; Dodge, O'Neal, Chang and Griffin, 1961). The experiments presented in this paper were designed to enquire once more into the role of the thyroid hormone in the pathogenesis of hepatomas. It was expected that findings obtained in hypophysectomized rats and in pituitary dwarf mice would be more amenable to interpretation than those obtained in intact or thyroidectomized rats and allow a sharper distinction between direct and indirect effects of the thyroid hormone to be made