EVALUATION OF THE RAT MICRONUCLEUS TEST WITH BONE-MARROW AND PERIPHERAL-BLOOD - SUMMARY OF THE 9TH COLLABORATIVE STUDY BY CSGMT JEMS-CENTER-DOT-MMS/

The mouse has traditionally been used For the micronucleus test, with bone marrow the usual target organ. The aim of the 9th collaborative s tudy by CSGMT was to evaluate the suitability of the rat for the micro nucleus test, with bone marrow and peripheral blood as the target orga n. Since the rat spleen eliminates circulating micronucleated erythroc ytes, a rat peripheral blood micronucleus assay might not be feasible. Thirty-Four Japanese laboratories and six overseas laboratories parti cipated in this collaboration, and 40 chemicals were studied. As a rul e, rat bone marrow and peripheral blood were analyzed using acridine o range staining. Among 36 mouse micronucleus-positive rat carcinogens, 34 of which had been evaluated by CSGMT, we observed 33 positive and t hree negative results with rat bone marrow and 30 positive, three equi vocal, and three negative responses with rat peripheral blood. OF the two mouse micronucleus-negative rot carcinogens, acrylonitrile was pos itive in rat bone marrow and 4,4'-methylene bis(2-chloroaniline) was n egative in both rat bone marrow and peripheral blood. Two chemicals re ported to be mouse micronucleus-negative and rat-positive, azobenzene and Solvent Yellow 14, and one chemical reported to be mouse-positive and rat-negative, 1,2-dimethylhydrazine, gave positive responses in ra t bone marrow and peripheral blood. The concordance between bone marro w and peripheral blood with rats was 92%. The concordance between rat and mouse erythrocytes was 88%. We concluded that the rat micronucleus assay, using either bone marrow or peripheral blood, can be used as a n alternative to the mouse micronucleus assay. Environ. Mol. Mutagen. 32:84-100, 1998 (C) 1998 Wiley-Liss, Inc.