SEVERAL observers have shown (Pfeiffer, Emmel and Gardner, 1940; Korenchevsky and Ross, 1940) that apart from the occasional production of urinary calculi and glomerulo-nephritis, prolonged oestrogen administration has only a slight effect on the kidneys of rodents, and never induces neoplasia. Matthews, Kirkman and Bacon (1947) were the first to demonstrate that the kidneys of the male golden hamster (Cricetus auratus) are the exception as they possess a peculiar susceptibility to renal neoplasia following treatment with oestrogen.The object of this communication is primarily to describe the histogenesis of these oestrogen-induced renal tumours in the male hamster, and to discuss other related problems which might help towards a better understanding of oestrogenic neoplasia. MATERIAL AND METHODS.Forty male golden hamsters, all approximately 12 weeks of age, each received a 20 mg. pellet of pure diethylstilboestrol subcutaneously in their right flank. An equal number of untreated male hamsters of the same group were kept as controls.For routine histological study the kidneys were fixed in alcoholic Bouin, and subsequently stained either in haematoxylin and eosin or by a modification of Masson's light green. In order to test for the presence of intracellular lipids, both fresh and formalin-fixed kidneys were stained with alkaline Sudan IV, Sudan black B and Nile blue sulphate. The pituitaries were fixed in Zenkerformol and differentially stained by Mallory's triple stain. Verhoeff's method was used for the staining of elastic fibres and the Gordon and Sweet procedulre for the presence of reticulin.OBSERVATIONS. Macroscopic description of renal turnours.Six and a half months after stilboestrol treatment had commenced all hamnsters were palpated weekly for the presence of kidney lesions.Although no renal tumours were palpable at this early period of treatment 8 hamsters were killed in order to study the development of early tumour formation. Each of these hamsters possessed very small cortical lesions which varied between 2 and 5 mm. in diameter. Small palpable tumours arose in some hamsters at the end of the 9th month of treatment, and by the beginning of the 11th month every treated hamster had large renal tumours. At the end of the 12th month
The significance of mitochondria in plant cells is a subject to which a great deal of attention has been paid in past years, and from the studies of many cytologists it has become apparent that these bodies are fundamentally concerned in the formation of many different substances in the cell. Fat droplets, anthocyanins, essential oils (28) and protein grains may all be quoted as examples of such substances (Cowdry, 5). Starch and other plastid products also appear to owe their origin indirectly to mitochondria; for it has been shown by various observers that plastids are in reality enlarged and transformed mitochondria, which take on the varying functions of the production of starch, chlorophyll, anthocyanins, fat, etc., according to whether they become amyloplasts, chloroplasts, chromoplasts, elaioplasts or other such protoplasmic structures. It seems, moreover, that these substances are originally formed within the mitochondria, which later enlarge to form the body of the plastids (Cowdry, 6). A suggested explanation of this productive activity of mitochondria is found in the eclectosome theory of Regaud (32), according to which mitochondria play the rôle of plasts, selecting materials from the cytoplasm, and fabricating them in their interior into various products. More in accord with known physicochemical processes, however, is the now generally accepted interpretation recently expressed by Cowdry (7), wherein the phase-boundary of the mitochondria and the surrounding cytoplasm is regarded as the seat of processes of elaboration, beginning with adsorption of the molecules of certain solutes, and ending with a series of chemical or physical interactions between the mitochondrial material and the incoming substances—such interactions leading to the building up of new compounds of widely different character.
IN a previous paper Horning (1954) reported the hormonal factors determining the successful transplantation of stilboestrol-induced renal tumours in the male golden hamster, the development of which was first described by Kirkman and Bacon (1949). Since then, these experiments on transplantation have been extended to provide additional evidence that renal neoplasia in the hamster comes under the category of hormonal cancer. The-results are discussed herein in the light of our present knowledge of endocrine neoplasia in other species of laboratory animals. MATERIAL AND METHODSMale golden hamsters of indeterminate ancestry bred in this Institute were used exclusively in these experiments. Primary kidney tumours were induced by implanting 20 mg. pellets of diethyl-stilboestrol subcutaneously in each animal. Each pellet was made from the pure synthetic hormone. They were moulded under pressure, and no binding medium was used. Each tablet was weighed prior to implantation, and each hamster received a second stilboestrol pellet 12 weeks after the first had been implanted. The period of induction between pellet implantation and the development of palpable kidney tumours was considerably reduced following treatment with the second tablet and the incidence of kidney tumours was also increased. Approximately 70 to 80 per cent of all male hamsters develop palpable renal lesions within 9 to 12 months following treatment with a single 20 mg. pellet, whereas the incidence following the introduction of the second is in some instances increased to 100 per cent. It is preferable, although not absolutely necessary, to select hamsters 6 to 8 weeks for this purpose.The most satisfactory way of obtaining successful transplantable renal tumours was to graft them subcutaneously into host animals which have been pre-treated with a 20 mg. tablet of stilboestrol 3 months prior to receiving the tumour implant. In another separate series of experiments both the stilboestrol pellet and the tumour were grafted simultaneously into normal hamsters which had not been previously treated with the synthetic hormone. The differences in the growth rates between the tumour grafts in these two series of experiments were then later compared.Tumours were also grafted into the subcutaneous tissues of the tail as well as into the flanks of pre-treated male hamsters. Selected pieces of the kidney tumour were finely minced up in saline, and approximately 0-2 ml. of this suspension was injected. The tail of the hamster is very small, and must be held firmly on a thick cork mat. The point of the syringe needle is then directed towards the tip of the tail, taking precaution to avoid the caudal vein.
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