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从短期和长期试验以及关于致癌性、致畸性和致突变性的研究中可以学到什么(作者译)

[What may be learnt from short- and long term tests and from studies on cancerogenicity, teratogenicity and mutagenicity (author's transl)].

作者信息

Frohberg H

出版信息

Arzneimittelforschung. 1977 Feb;27(2A):228-41.

PMID:577168
Abstract

During the last 15 years the transferability of results from animal experiments to humans has been improved so that today certainly more than 70% of possible side effects can be predicted. Systemic hypersensitivity reactions cannot be predicted, however, since to date there are no safe animal experimental methods available. In spite of many decades of research in the field of animal experimental cancerogenesis the value of investigations of this kind for humans can be limited by the selection of unsuitable animal species, use of inadequate modes of administration or excessive doses. Similar aspects apply to reproduction toxicology; there are many examples in cancerology and teratology for false-positive and -negative results from animal experiments. In chemomutagenesis comparisons of in vivo cytogenetic investigations in somatic cells of animals and humans have revealed largely concurring results. However, only stable mutations found in generative cells are signs of a genetic danger. It will therefore have to be clarified which conclusions for generative cells should be drawn from changes in somatic cells. Furthermore, the elaboration of methods for the determination of the mutation of genes in the organism of mammals still requires intensive research.

摘要

在过去15年里,动物实验结果向人类的可转移性有所提高,以至于如今肯定能预测超过70%的可能副作用。然而,全身性过敏反应无法预测,因为迄今为止尚无可用的安全动物实验方法。尽管在动物实验致癌领域进行了数十年研究,但这类研究对人类的价值可能因选择不合适的动物物种、使用不适当的给药方式或过量剂量而受到限制。类似情况也适用于生殖毒理学;在癌症学和致畸学中有许多动物实验出现假阳性和假阴性结果的例子。在化学诱变方面,对动物和人类体细胞进行的体内细胞遗传学研究比较显示出结果基本一致。然而,只有在生殖细胞中发现的稳定突变才是遗传危险的迹象。因此,必须弄清楚应从体细胞变化中得出哪些关于生殖细胞的结论。此外,完善用于测定哺乳动物体内基因突变的方法仍需要深入研究。

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