The micronucleus test. Methodological aspects

Changes in the cellular compositiion of bone marrow were studied in relation to dose of Trenimon® and time after treatment. Strong mutagenic effects caused a partial depletion of the marrow cavities of nucleated blood cell precursors, with subsequent retention of newly formed erythrocytes and inundation with peripheral blood. The influence of these changes on the results of micronucleus scoring was investigated in a time-effect and a dose-effect study using three different methods of evaluation, relating the incidence of micronuclei to (a) nucleated cells, (b) all erythrocytes, and (c) polychromatic erythrocytes. Conclusions are drawn on the practical use of the micronucleus test system. The simplest scoring procedure, namely relating micronucleated polychromatic erythrocytes to a given total number of erythrocytes, was very efficient in the range of low mutagenic effects and therefore well suited for safety screening wherease dose-effect studies comprising very high mutagenic effects required the application of a modified method of scoring.