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首页> 外文期刊>Mutation Research: International Journal on Mutagenesis, Chromosome Breakage and Related Subjects >Genotoxicity testing of biotechnology-derived products. Report of a GUM task force.Gesellschaft fur Umweltmutationsforschung.
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Genotoxicity testing of biotechnology-derived products. Report of a GUM task force.Gesellschaft fur Umweltmutationsforschung.

机译：生物技术衍生产品的基因毒性测试。 GUM工作组的报告。Gesellschaftfur Umweltmutationsforschung。

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Various aspects of genotoxicity testing of biotechnology-derived products are discussed based on information gathered from a questionnaire which was sent to about 30 predominantly European companies. Feedback was received from 13 companies on 78 compounds, mostly recombinant proteins but also on a number of nonrecombinant proteins, which had been assessed for genotoxicity in a total of 177 tests. Four of the 78 compounds appeared to elicit reproducible genotoxic effects. For one of these compounds, the activity could be related to a nonpeptidic linker molecule. No scientifically convincing rationale for the other three compounds could be established, although, at least for two compounds, their activity may be connected with the enzymatic/hormonal activity. In addition to the survey, published reports on genotoxicity testing of biotechnology products were reviewed. The data are discussed relative to whether genotoxicity testing is a valuable exercise when assessing potentially toxic liabilities of biotechnology-derived compounds. It is concluded that genotoxicity testing is generally inappropriate and unnecessary, a position which is in accordance with the available guidelines addressing this area. For the 'average' protein, electrophilic reactions are difficult to envision. Indirect reactions via DNA metabolism and growth regulation seem possible for only very specific proteins such as nucleases, growth factors, cytokines. No information on testing of different types of biotechnology-derived products (e.g., ribozymes, antisense-oligonucleotides, DNA vaccines) has been received in the questionnaires. Discussion of their potential to cause genotoxic changes was based on literature reports. Even for those products for which concerns of genotoxic/tumourigenic potential cannot be completely ruled out, e.g., because of their interaction with DNA metabolism or proliferation control, the performance of standard genotoxicity assays generally appears to be of little value. All information, including also information on the occurrence of genotoxic impurities, has been utilized to formulate a decision tree approach for the genotoxicity testing of biotechnology-derived products. Copyright 1999 Elsevier Science B.V.
机译：基于从调查表收集的信息，讨论了生物技术衍生产品的遗传毒性测试的各个方面，该调查表已发送给大约30家主要是欧洲公司。从13家公司收到了关于78种化合物的反馈，这些化合物主要是重组蛋白，还涉及许多非重组蛋白，这些蛋白已通过177项测试进行了遗传毒性评估。 78种化合物中有4种似乎引起可再生的遗传毒性作用。对于这些化合物之一，活性可能与非肽接头分子有关。尽管至少对于两种化合物而言，其活性可能与酶/激素活性有关，但无法确定其他三种化合物的科学依据。除调查外，还审查了有关生物技术产品遗传毒性测试的已发表报告。在评估生物技术衍生化合物的潜在毒性负债时，讨论了有关基因毒性测试是否是有价值的练习的数据。结论是，遗传毒性测试通常是不适当的和不必要的，其位置符合针对该领域的可用指南。对于“平均”蛋白质，亲电反应很难预料。通过DNA代谢和生长调节的间接反应似乎仅可能用于非常特殊的蛋白质，例如核酸酶，生长因子，细胞因子。问卷中没有收到有关测试不同类型的生物技术衍生产品（例如核酶，反义寡核苷酸，DNA疫苗）的信息。根据文献报道对它们引起遗传毒性变化的潜力进行了讨论。即使对于那些不能完全排除遗传毒性/致瘤潜力的产品，例如由于它们与DNA代谢或增殖控制的相互作用，标准遗传毒性试验的执行通常似乎也没有什么价值。所有信息，包括有关遗传毒性杂质发生的信息，已被用于制定决策树方法，用于生物技术衍生产品的遗传毒性测试。版权所有1999 Elsevier Science B.V.

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