EVALUATION OF BENOMYL AND CARBENDAZIM IN THE IN-VIVO ANEUPLOIDY MICRONUCLEUS ASSAY IN BDF1 MOUSE BONE-MARROW/

Benomyl and its active metabolite carbendazim were investigated in BDF 1 mouse bone marrow to establish whether micronuclei induced by these fungicides are caused by clastogenic or aneugenic events. Micronuclei were evaluated for kinetochores using immunofluorescent antikinetochor e antibodies. Kinetochore positive (K+) micronuclei are likely to aris e from chromosome loss since they presumably contain intact kinetochor es and are indicative of aneuploidy. Conversely, kinetochore negative (K-) micronuclei are most likely to contain acentric chromosome fragme nts arising primarily from clastogenic damage. Benomyl and carbendazim were administered as single oral doses of 0.3, 8.6 or 17.2 mmol/kg (f or benomyl, equivalent to 100, 2500 or 5000 mg/kg; for carbendazim, eq uivalent to 66, 1646 or 3293 mg/kg). Both compounds were positive in t he micronucleus test at doses of 8.6 and 17.2 mmol/kg, and an average of 82% (benomyl) and 87% (carbendazim) of the total micronucleated pol ychromatic erythrocytes were K+. No effects were seen with either fung icide at 0.3 mmol/kg. These results are analogous to findings with kno wn aneugens such as vincristine but are in contrast to results with cl assical clastogens such as cyclophosphamide. Thus, benomyl and carbend azim induce micronuclei in mouse bone marrow cells primarily through a n aneugenic mechanism.