Critical appraisal of the 'mouse testicular DNA-synthesis inhibition test' for the detection of mutagens and carcinogens.

A short test (DSI test) in vivo for the identification of environmental mutagens and carcinogens was recently published by Friedman and Staub (1976), and Seiler (1977). The test is based on the measurements of [3H]thymidine incorporation into murine testicular DNA. This incorporation was inhibited by a number of mutagens and carcinogens when given at high doses. However, under such conditions, many chemicals are known to cause hypothermia in mice, which may itself lead to a reduced [3H]thymidine incorporation. We therefore investigated the effect of a few non-mutagenic and mutagenic test substances on the incorporation of [3H]thymidine into testicular DNA and on changes in body temperature. We also studied the effect of reduced testicular temperature, caused by physical means, on the incorporation of [3H]thymidine into DNA. 3 mutagens out of 4, and 6 non-mutagens out of 6, caused hypothermia in mice, and at the same time inhibited [3H]thymidine incorporation. This parameter also changed as the testicular temperature was reduced, indicating an obvious correlation between the 2 effects. Furthermore, we found that, with some of the test substances, a reduction of [3H]thymidine incorporation into DNA can be compensated under isothermal conditions. We believe that the DSI test is not reliable as a screening system for the identification of potential mutagens and cancerogens because of the unspecificity of the parameter measured.