The purpose of the unscheduled DNA synthesis (UDS) test with mammalian liver cells in vivo is to identify substances that induce DNA repair after excision and removal of a stretch of DNA containing a region of damage induced by chemical substances (solid or liquid) or physical agents in the liver.
The test is usually based on the incorporation of tritium-labelled thymidine, 3H-TdR, (during 3-8 hours) into the DNA of liver cells which have a low frequency of cells in the S-phase of the cell cycle. The uptake of 3H-TdR is usually determined by autoradiography. Rats are commonly used, and the number of animals should be at least three analysable animals per group. Normally, at least two dose levels are used. A limit test may be performed if no effects would be expected at a dose of 2000 mg/kg bw/d. Test substances are generally administered as a single treatment by gavage using a stomach tube or a suitable intubation cannula. Liver cells are prepared from treated animals 12-16 hours after dosing of animal. After autoradiography, normally 100 cells are scored from each animal from at least two slides. A positive result from the UDS test with mammalian liver cells in vivo indicates that a substance induces DNA damage in mammalian liver cells in vivo that can be repaired by unscheduled DNA synthesis in vitro. A negative result indicates that, under the test conditions, the test substance does not induce DNA damage that is detectable by this test.
