The in vivo gut micronucleus test detects clastogens and aneugens given by gavage.

Abstract

A general testing battery for pharmaceuticals includes a bacterial gene mutation assay, an in vitro chromosomal aberration or a gene mutation test on mammalian cells and an in vivo test for chromosome/genome mutations. The aim of this study was to determine whether the in vivo mouse gut micronucleus assay could be a more sensitive method to detect direct clastogens and/or aneugens given orally by gavage than the in vivo bone marrow micronucleus assay (which can also detect indirect genotoxins). Two laboratories collaborated in this project, one analysing bone marrow cells and the other analysing gut cells from the same animals. The reference substances tested in this study were colchicine (COL), carbendazim (CAR), tubulazole (TUB) and griseofulvin (GRI), all known aneugens, and 1,2-dimethylhydrazine (DMH), a colon carcinogen with clastogenic activity. For all substances tested, the in vivo gut micronucleus test was as sensitive as or more sensitive than the in vivo bone marrow micronucleus assay: COL and TUB induced micronuclei in both 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 able to detect clastogens and aneugens given orally by gavage, some of which were not detected by the bone marrow micronucleus test.