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首頁> 美國衛(wèi)生研究院文獻>Environmental Health Perspectives >Hazard identification: efficiency of short-term tests in identifying germ cell mutagens and putative nongenotoxic carcinogens.
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Hazard identification: efficiency of short-term tests in identifying germ cell mutagens and putative nongenotoxic carcinogens.

機譯:危害識別:識別生殖細胞誘變劑和推定的非遺傳毒性致癌物的短期測試的效率。

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摘要

For more than a decade, mutagenicity tests have had a clearly defined role in the identification of potential human mutagens and an ancillary role in the identification of potential human carcinogens. The efficiency of short-term tests in identifying germ cell mutagens has been examined using a combined data set derived from the U.S. Environmental Protection Agency/International Agency for Research on Cancer Genetic Activity Profile (EPA/IARC GAP) and EPA Gene-Tox databases. Our review of these data indicates adequate sensitivity of batteries of in vitro short-term mutagenicity tests in identifying germ cell mutagens. The analysis also supports the inclusion of an in vivo assay as suggested in proposed regulatory testing guidelines. In the context of carcinogenicity testing, the ability of short-term bioassays to detect genotoxic or mutagenic carcinogens is well established. Such tests are not considered to be as sensitive to nongenotoxic or nonmutagenic carcinogens. However, analyses presented in this report using the EPA/IARC GAP database demonstrate that many putative nongenotoxic carcinogens that have been adequately tested in short-term genetic bioassays induce gene or chromosomal mutation or aneuploidy. Further investigation should reveal whether the mutagenicity of these agents plays an important mechanistic role in their carcinogenicity.
機譯:十多年來,致突變性測試在鑒定潛在的人類誘變劑中具有明確定義的作用,在鑒定潛在的人類致癌物方面具有輔助作用。已經(jīng)使用美國環(huán)境保護署/國際癌癥遺傳活性譜研究機構(gòu)(EPA / IARC GAP)和EPA Gene-Tox數(shù)據(jù)庫的組合數(shù)據(jù)集對鑒定生殖細胞誘變劑的短期測試的效率進行了檢查。我們對這些數(shù)據(jù)的審查表明,體外短期致突變性測試對鑒定生殖細胞誘變劑具有足夠的敏感性。該分析還支持提議的監(jiān)管測試指南中建議的體內(nèi)分析。在致癌性測試的背景下,已經(jīng)建立了短期生物測定法檢測遺傳毒性或致突變性致癌物的能力。此類測試不被視為對非遺傳毒性或非誘變致癌物敏感。但是,本報告中使用EPA / IARC GAP數(shù)據(jù)庫進行的分析表明,已在短期遺傳生物測定法中經(jīng)過充分測試的許多假定的非遺傳毒性致癌物均會誘導基因或染色體突變或非整倍性。進一步的研究應揭示這些試劑的致突變性是否在其致癌性中起重要的機械作用。

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