Rapid Liver Tumour Induction by Concerted Action of N-Hydroxy-2-acetamidofluorene and Hormonal Stimulation

Abstract

LIVER is not usually considered a target organ of hormonal factors known at present. Nevertheless, in certain animal species, the operation of such agents is clearly evident. Thus, liver cancer induction by certain carcinogenic azo dyes occurs more readily in female than in male mice. With certain other azo dyes¹, and with 2-acetamidofluorene² and its probable proximate agent N-hydroxy-2-acetamidonuorene³, male rats are considerably more susceptible than females. Liver carcinogenesis is enhanced by the joint administration of anabolic hormones, testosterone or cortisone, and 2-acetamidofluorene, its diacetyl derivative⁴ or its N-hydroxy derivative⁵. Castration of female rats and joint administration of testosterone and 2-diacetamidofluorene gave rise to liver tumours to almost the same extent as in male rats⁶. Whether these hormonal factors act directly or by way of alteration of the total hormonal balance involving the pituitary, gonads, adrenals and target organ is, at present, not known. Surgical removal of the adrenals or of the pituitary gland delays or abolishes carcinogenesis in the liver by azo dye or the carcinogenic fluorene derivatives (see ref. 7). Participation of hormonal factors derived from the pituitary in the carcinogenic process in the liver might therefore be surmised. However, direct evidence on this point has so far not been adduced. Bielschowsky⁸, Laws⁹, and also Glinos et al.¹⁰, have attempted to devise experiments to establish a multiple stage mechanism for liver carcinogenesis, but their observations were either negative or at best suggestive for the operation of such a process.