The in vivo gut micronucleus test detects clastogens and aneugens given bygavage

A general testing battery for pharmaceuticals includes a bacterial gene mut ation assay, an irt vitro chromosomal aberration or a gene mutation test on mammalian cells acid an in vivo test for chromosome/genome mutations. The aim of this study was to determine whether the in vivo mouse gut micronucle us assay could be a more sensitive method to detect direct clastogens and/o r aneugens given orally by gavage than the in vivo bone marrow micronucleus assay (which can also detect indirect genotoxins). Two laboratories collab orated in this project, one analysing bone marrow cells and the other analy sing gut cells from the same animals. The reference substances tested in th is study were colchicine (COL), carbendazim (CAR), tubulazole (TUB) and gri seofulvin (GRI), all known aneugens, and 1,2-dimethylhydrazine (DMH), a col on carcinogen with clastogenic activity. For all substances tested, the in vivo gut micronucleus test was as sensitive as or more sensitive than the i n vivo bone marrow micronucleus assay: COL and TUR induced micronuclei in b oth gut and bone marrow cells; DMH, CAR and GRI induced micronuclei only in gut cells. The results show that the micronucleus test on gut cells is abl e to detect clastogens and aneugens given orally by gavage, some of which w ere not detected by the bone marrow micronucleus test.