Waters M D, Stack H F, Jackson M A, Bridges B A
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Environ Health Perspect. 1993 Oct;101 Suppl 3(Suppl 3):61-72. doi: 10.1289/ehp.93101s361.
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.
十多年来，致突变性试验在识别潜在人类诱变剂方面具有明确界定的作用，在识别潜在人类致癌物方面发挥辅助作用。利用来自美国环境保护局/国际癌症研究机构遗传活性概况（EPA/IARC GAP）和EPA基因毒性数据库的综合数据集，对短期试验识别生殖细胞诱变剂的效率进行了研究。我们对这些数据的审查表明，体外短期致突变性试验组合在识别生殖细胞诱变剂方面具有足够的敏感性。该分析还支持按照拟议的监管测试指南的建议纳入体内试验。在致癌性测试方面，短期生物测定检测遗传毒性或致突变性致癌物的能力已得到充分证实。此类试验被认为对非遗传毒性或非致突变性致癌物不那么敏感。然而，本报告中使用EPA/IARC GAP数据库进行的分析表明，许多在短期遗传生物测定中经过充分测试的推定非遗传毒性致癌物会诱导基因或染色体突变或非整倍体。进一步的研究应揭示这些物质的致突变性在其致癌性中是否发挥重要的机制作用。
