Unscheduled DNA synthesis tests. A report of the U.S. Environmental Protection Agency Gene-Tox Program

• Published in: Mutation research Vol. 123; no. 3; p. 363
• Main Authors: Mitchell, A D, Casciano, D A, Meltz, M L, Robinson, D E, San, R H, Williams, G M, Von Halle, E S
• Format: Journal Article
• Language: English
• Published: Netherlands 01.12.1983
• Subjects: Animals; Autoradiography - methods; DNA Replication - drug effects; Dose-Response Relationship, Drug; Fibroblasts - drug effects; Humans; Liver - drug effects; Liver - metabolism; Mutagenicity Tests - methods; Mutagens - toxicity; Mutation; Rats; Tritium; United States; United States Environmental Protection Agency; United States
• ISSN: 0027-5107

The utility of unscheduled DNA synthesis (UDS) testing for screening potentially hazardous chemicals was evaluated using the published papers and technical reports available to the UDS Work Group. A total of 244 documents were reviewed. Based on criteria defined in advance for evaluation of the results, 169 were rejected. From the 75 documents accepted, results were reviewed for 136 chemicals tested using autoradiographic approaches and for 147 chemicals tested using liquid scintillation counting (LSC) procedures; 38 chemicals were tested by both approaches to measure UDS. Since there were no documents available that provided detailed recommendations of UDS screening protocols or criteria for evaluating the results, the UDS Work Group presents suggested protocols and evaluation criteria suitable for measuring and evaluating UDS by autoradiography in primary rat hepatocytes and diploid human fibroblasts and by the LSC approach in diploid human fibroblasts. UDS detection is an appropriate system for inclusion in carcinogenicity and mutagenicity testing programs, because it measures the repair of DNA damage induced by many classes of chemicals over the entire mammalian genome. However, for this system to be utilized effectively, appropriate metabolic activation systems for autoradiographic measurements of UDS in human diploid fibroblasts must be developed, the nature of hepatocyte-to-hepatocyte variability in UDS responses must be determined, and the three suggested protocols must be thoroughly evaluated by using them to test a large number of coded chemicals of known in vivo mutagenicity and carcinogenicity.