MICRONUCLEUS MORPHOLOGY AS A MEANS TO DISTINGUISH ANEUGENS AND CLASTOGENS IN THE MOUSE BONE-MARROW MICRONUCLEUS ASSAY

Detailed dose-response data for two reference aneugens, vincristine and nocodazole, have been derived for the mouse bone marrow micronucleus assay. Positive data have also been described for six other micronucleus-inducing agents: cyclophosphamide; aniline; urethane; 1,2-dimethylhydrazine; 7,12-dimethylbenzanthracene and procarbazine. Micronuclei (MN) were classified according to the morphological criteria listed by Yamamoto and Kikuchi, i.e. normal, double, multiple, ring, crescent and large. Aniline and control slides exhibited low incidences of aberrant MN (< 3%). The remaining seven chemicals gave incidences of aberrant MN that varied from 3 to 25%. Only the aneugens vincristine and nocodazole, and the possible aneugen urethane, gave both crescent shaped and large MN (> 0.25 cell diameter). It is therefore concluded that only these last two classes of aberrant MN can be taken as indicative of aneugenic activity. Vincristine and nocodazole gave the highest incidences of aberrant MN and these were shown to be strongly dose-related in the case of vincristine.