DNA repair assays as tests for environmental mutagens. A report of the U.S. EPA Gene-Tox Program

A literature review was undertaken to determine the usefulness of DNA repair assays, other than unscheduled DNA synthesis, as screening techniques for mutagenic carcinogens. 92 reports were found to contain useful data for 49 chemicals using 6 techniques, namely, (1) cesium chloride equilibrium density gradients to study repair replication, (2) benzoylated naphthoylated diethylaminoethyl cellulose columns to study repair replication, (3) 313-nm irradiation of DNA containing bromodeoxyuridine to study repair replication, (4) alkaline elution to study repair of single-strand breaks and crosslinks, (5) alkaline sucrose gradients to study repair of single-strand breaks, and (6) direct assays for removal of adducts from DNA. Almost all of the 49 chemicals studied were known mutagens or carcinogens and/or known inducers of DNA repair, 9 compounds failed to elicit DNA repair by at least 1 assay technique, and at least 3 of these were not tested by the most appropriate and sensitive method. Nevertheless, although valid for studying repair phenomena in eukaryotic cells, these assays are not considered useful for screening. They are time-consuming, expensive, and/or require highly specialized skills. Despite the high frequency of positive reports, it is obvious from the literature that repair assays will fail to detect, or will detect with low efficiency, those agents whose main action is either intercalation or induction of strand breaks. For these and other reasons, DNA repair as a basis for screening for mutagenic carcinogens is not considered to be a useful concept.