Studies on micronuclei time response and on the effects of multiple treatments of mutagens on induction of micronuclei.

Micronuclei time response and the effects of multiple treatments of mutagens on induction of micronuclei were studied. In the time-response investigation, mice were treated once with each of 5 mutagens, then killed at various times. The bone marrow was examined for the presence of micronucleated erythrocytes (MNEs). The maximal frequencies for MNEs occurred around 30 h post treatment for all mutagens tested. To examine the effects of multiple treatments, the frequencies of MNEs observed after a single- or a 5-treatment schedule were compared for 9 mutagens. Both treatment schedules were equally sensitive in detecting alkylating agents and spindle poisons, whereas the 5-treatment schedule was more sensitive for anti-metabolites. The 5-treatment schedule was particularly effective for detecting the anti-metabolites 5-fluorouracil and methotrexate, which require longer than 30 h to induce micronuclei (Maier and Schmid, 1976). These results suggest that it is practicable to sample at 30 h in the single-treatment schedule, and seem to support the usefulness of the 5-treatment schedule in screening tests.