Science Inventory

Identification of Potential Germ-Cell Mutagens

Citation:

DeMarini, D. Identification of Potential Germ-Cell Mutagens. 9th Congress of the Society of Toxicology of Developing Countries and the 19th Congress of the Society of Toxicology of Brazil, Natal and Rio de Janeiro, BRAZIL, November 06 - 10, 2015.

Impact/Purpose:

Dr. DeMarini has been invited to two activities: (1) invited speaker at the 9th Society of Toxicology of Developing Countries and 19th Society of Toxicology Brazil meetings, which are being held jointly in Natal, Brazil. This combined conference will bring together scientists from developing and developed countries to share important information on emerging scientific issues, including the possible role of air pollution as a germ-cell mutagen. (2) the second event is an invitation to speak at the Brazilian National Cancer Institute (INCA), which is Rio de Janeiro. Dr. DeMarini will speak on cookstove research he and his team are involved in. The abstract for that talk is identical to one approved recently for conference in Athens, Georgia, and also in Plymouth, England. Both are attached. Cookstoves and associated health effects are an important issue in Brazil and of concern to the Brazilian National Cancer Institute. Dr. DeMarini will have the opportunity to show the work that the U.S. EPA is doing in this area.

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. Various rodent-based germ-cell mutation assays have been developed, and ~50 germ-cell mutagens have been identified in these assays; however, no agent has been declared a germ-cell mutagen in humans. Nonetheless, evidence is emerging that ionizing radiation, air pollution, and tobacco smoke may be human germ-cell mutagens. Rodent assays for germ-cell mutagens have been incorporated into testing guidelines by the IPCS/WHO Harmonized Scheme for Mutagenicity Testing and by the OECD, and regulatory agencies in North America and Europe. The dominant lethal assay (DL) and the spermatogonia chromosome aberration assay (SCA) are the ones in current use, usually involving treatment of males. An assay for gene mutation in sperm of transgenic rodents is also an OCED-approved assay but detects mutations in germ cells rather than in pedigrees. The DL assay detects mutation in male germ cells, usually large deletions; however, it is expensive, time consuming, and labor intensive. The SCA assay typically involves the scoring of 100 metaphases per animal (500/group) for chromosome aberrations. Because these assays are performed in rodents, the results are considered to have relevance to humans. Nonetheless, there are now new assays that, although not yet validated, could be used to detect an array of germ-line mutations in humans, including copy-number variant analysis and whole-genome sequencing. [Abstract does not necessarily reflect the views or policies of the U.S. EPA.]

Record Details:

Record Type:DOCUMENT( PRESENTATION/ ABSTRACT)
Product Published Date:11/10/2015
Record Last Revised:11/13/2015
OMB Category:Other
Record ID: 310229