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Are There Human Germ-Cell Mutagens? We May Know Soon
Citation:
DeMarini, D. Are There Human Germ-Cell Mutagens? We May Know Soon. Genetics and Environmental Mutagenesis Society, RTP, NC, October 28, 2015.
Impact/Purpose:
This is an overview, invited lecture for the Genetics and Environmental Mutagenesis Society (GEMS) in October 2015 at the NC Biotechnology Center in RTP, NC. This talk provides an overview of the current state of evaluating agents as human germ-cell mutagens, and these include air pollution.
Description:
The existence of agents that can induce germ-cell mutations in experimental systems has been recognized since 1927 with the discovery of the ability of X-rays to induce such mutations in Drosophila. Since then, various rodent-based assays have been used to identify ~50 germ-cell mutagens, as summarized in a workshop organized by the Environmental Mutagenesis and Genomics Society (EMGS) and the Jackson Laboratory (Wyrobek et al., EMM 48:71, 2007). Although no agent has been declared a germ-cell mutagen in humans, I used criteria similar to those of IARC for evaluating human carcinogens and identified four classes of agents as human germ-cell mutagens: chemotherapy, ionizing radiation, cigarette smoke, and urban air pollution (Environ Mol Mutagen 53:166, 2012). Consequently, the EMGS organized a working group called ENvironmentally Induced Germline Mutation Analysis (ENIGMA) to encourage the application of new genomic technologies to assess environmental influences on inherited diseases (Yauk et al., Mutat Res 752:6, 2013). The OECD has begun developing a series of Adverse Outcome Pathways (AOPs) on germ-cell mutagenicity to identify new technologies to assess germ-cell mutation that can fit into the rapidly evolving paradigm for toxicity testing (Yauk et al., Mutat Res 54:79, 2013; Yauk et al., Mutat Res, in press, 2015). A recent International Workshop on Genotoxicity Testing (IWGT) addressed current data gaps in the field, identified tools to fill these gaps, and proposed new models for when and how germ-cell mutagenicity testing should be conducted (Yauk et al., Mutat Res 783:36, 2015). In November 2017, IARC will host a scientific meeting to evaluate several agents as human germ-cell mutagens, presenting the possibility that an international organization may finally declare the existence of human germ-cell mutagens 90 years after the discovery of the first germ-cell mutagen. [Abstract does not necessarily reflect the views or policies of the U.S. EPA.]