Enzootic and Epizootic Adrenal Medullary Proliferative Disease of Rats: Influence of Dietary Factors which Affect Calcium Absorption

Abstract

<jats:p> Adrenal medullary hyperplasia and neoplasia occur both enzootically and epizootically in untreated laboratory rats. The lesions are typically chromaffin-negative and are found incidentally in animals that have died from unrelated causes or have been killed at the end of long-term toxicity/ carcinogenicity tests. Urinary excretion of catecholamines is not usually increased. Environmental, particularly dietary, factors are seemingly much more important than genetic ones as determinants of the incidence of proliferative lesions. Recent observations of enhancement of adrenal medullary proliferative disease in rats by the feeding, in high dietary concentration, of certain polyols (sorbitol, mannitol, xylitol, lactitol), or of lactose, suggested that increased absorption of calcium from the gastrointestinal tract may be a risk factor. This evidence is reported and discussed in the light of other evidence linking disturbed calcium homeostasis with adrenal medullary function in the rat. </jats:p><jats:p> In man, adrenal medullary proliferative disease is relatively rare and there is no evidence of any relation between the hypercalcaemia associated with hyperparathyroidism and increased risk of phaeochromocytoma. Adrenal medullary proliferative disease in rats is usually seen against a background of multiple endocrine neoplasia, with the pituitary gland, the pancreatic islets and the thyroid C-cells being most commonly affected in addition to the adrenal medulla. A parallel between this situation and Sipple's disease in humans has previously been suggested. </jats:p><jats:p> We now stress the possible importance of three factors as determinants of enzootic and epizootic adrenal medullary proliferative disease in rats: excessive food intake, excessive dietary levels of calcium and phosphate and excessive intake of other food components, such as vitamin D and poorly absorbable carbohydrates, which predispose to increased calcium absorption. </jats:p>

The Influence of Food Additives and Related Materials on Lower Bowel Structure and Function

“…These medullary changes have been reported recently and in the past several years (1,3,9,13,15,16,25). Moreover, such lesions are common, but variable in incidence, in aging rats (9).…”

“…Moreover, reducing dietary calcium decreases the incidence of adrenal changes associated with xylitol (Table IX). (24,25) that chemicallymodified starches, lactose, and a number of the sugar alcohols all cause increased calcium absorption, and, in rodents, enlargement of the cecum with or without renal mineralization. The hypercalcemia.…”

The predictive value of pathological findings in animal toxicity studies.

“…Various sugar alcohols, neuroleptics, nicotine, growth hor mone, and lactose are among the agents known to induce these tumours in the rat. Disturbances of carbohydrate metabolism, calcium homeostasis, and hormonal inbalances are discussed as possible associated factors (Roe and Bar 1985)31. Reduc tion of carbohydrates in the diet reduces the inci dence of adrenal medullary tumours in the rat (Gilbert et al, 1958)11.…”

Acetaldehyde and Formaldehyde: Is There a Cancer Risk for Man?

“…This would explain why excessive exposure to non-genotoxic natural hormones predisposes to increased cancer risk in hormone-respon sive tissues. Also, it would explain why natural non-geno toxic food ingredients such as lactose can predispose to adrenal medullary neoplasia in rats [31]. It raises the question of which factor is more important in relation to the association between smoking and lung cancer; is it the presence of low levels of genotoxins in the smoke or could it be that irritation and resulting increased cellular prolif eration in the epithelium of the respiratory tract plays a more important role?…”