Appropriate in vitro test conditions for genotoxicity testing of fibers.
With the exception of asbestos fibers, little information is available on genotoxicity testing of fibers (i.e., respirable-sized, fiber-shaped particulates, RFP). In contrast to standard genotoxicity testing of soluble substances, fibers bring about specific problems. Test results can be influenced by fiber dimensions, surface properties, and biopersistence. The mechanisms of fiber-induced genotoxicity are not yet clear, but direct interaction with the genetic material and indirect effects via production of reactive oxygen species (ROS) have been proposed. Asbestos did not significantly induce gene mutations in bacterial and mammalian systems but led to a clear induction of structural and numerical chromosome aberrations in cultured mammalian cells. It is the purpose of this article to critically review positive in vitro genotoxicity data obtained for asbestos in the comet assay, the chromosome aberration test, and the micronucleus test and to identify the test conditions that are specifically required for the detection of asbestos-induced genotoxicity. It is concluded that appropriate cell systems are available for testing fiber-induced genotoxicity. Fiber samples have to be well characterized and phagocytosis and cytotoxic effects have to be determined for the correct interpretation of genotoxicity test results. A combination of the micronucleus test and the comet assay using continuous treatment (without exogenous metabolic activation) seems to be well suited to detect genotoxic activity of asbestos fibers with high accuracy. Further investigations are needed to shown whether this approach can be recommended for genotoxicity testing of fibers in general.
Universitätsklinikum Ulm, Abteilung Humangenetik, D-89070 Ulm, Germany. guenter.speit@medizin.uni-ulm.de
Günter
G
Speit
D001194:Asbestos / Q000737:chemistry / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects; D008168:Lung / Q000187:drug effects*; D009152:Mutagenicity Tests
D001194:Asbestos