Carcinogenicity studies in animals relevant to the use of anabolic agents in animal production.

F J Rose
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Abstract

It has long been known that certain estrogens and testosterone may increase, or sometime decrease, the incidence of neoplasmas in laboratory animals. They probably act by switching-on inappropriate genetic information or switching-off appropriate genetic information contained in nucleic acids. For instance, they may switch-on in adult animals information which is relevant only to a certain stage of embryogenesis or they may facilitate the expression of oncogenic viruses which would otherwise lay harmlessly dormant. The situation is rendered complex because an effect on one endocrine gland leads to effects on others so that factors which favour tumour development may result indirectly from administration of an anabolic or other hormonal agent. Two kinds of neoplasm are now known to be associated with human exposure to anabolic agents: vaginal adenocarcinoma and liver-cell tumours. Tumours of both kinds are among the spectrum of neoplasms that has been seen in laboratory animals exposed to agents of the same kind. In both animals and man there is evidence that tumours arising in response to anabolic agents are sometimes, initially at least, hormone-dependent. The evidence that 17beta-estradiol, diethylstilbestrol, chlormadinone, and testosterone are carcinogenic for laboratory animals is briefly reviewed and the reader's attention is directed towards the 1974 IARC Monograph on the evaluation of sex hormones for carcinogenic risk to man where the same evidence is reviewed more extensively. The significance for man of the results of studies on laboratory animals is discussed with special reference to the use of anabolic agents in meat production. Non-residue uses are to be preferred, as are naturally-occurring agents as opposed to compounds which do not occur in nature. More information is needed concerning the possible effects of prolonged exposure to very low doses of anabolic agents.

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与动物生产中使用合成代谢剂有关的动物致癌性研究。
人们早就知道,在实验动物中,某些雌激素和睾酮可能会增加或有时会减少肿瘤的发病率。它们可能通过开启不合适的遗传信息或关闭核酸中包含的合适的遗传信息来起作用。例如,它们可能在成年动物中开启仅与胚胎发生的某一阶段有关的信息,或者它们可能促进致癌病毒的表达,否则这些病毒将处于无害的休眠状态。情况变得复杂,因为对一个内分泌腺的影响会导致对其他内分泌腺的影响,因此有利于肿瘤发展的因素可能间接地由合成代谢或其他激素制剂引起。目前已知有两种肿瘤与人体暴露于合成代谢剂有关:阴道腺癌和肝细胞肿瘤。这两种肿瘤都属于已在实验动物中发现的暴露于同类物质的肿瘤谱系。在动物和人身上都有证据表明,对合成代谢剂产生的肿瘤有时(至少在最初)是依赖于激素的。本文简要回顾了17 -雌二醇、己烯雌酚、氯麦地那酮和睾酮对实验动物具有致癌性的证据,读者应注意1974年IARC关于性激素对人类致癌风险评估的专著,该专著对同样的证据进行了更广泛的审查。讨论了实验动物研究结果对人类的意义,特别提到了在肉类生产中使用合成代谢剂。无残留用途是优选的,因为是天然存在的剂,而不是在自然界中不存在的化合物。关于长期暴露于极低剂量的合成代谢剂可能产生的影响,需要更多的资料。
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Plasma levels and secretion rate of steroids with anabolic activity in man. An approach to the anabolic action of androgens by an experimental system. Epidemiological studies related to the use of hormonal agents in animal production. Pharmacological and endocrinological studies on anabolic agents. Role of growth hormone in improving animal production.
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