An in vivo assay for small intestine genotoxicity

The induction of nuclear aberrations (NA) (apoptotic bodies and micronuclei) in duodenal crypts in a dose-dependent manner was associated with administration of agents known to induce tumours in the small intestine. These included X-irradiation, N-methyl-N-nitrosourea (MNU), benzo[a]pyrene (B[a]P), and 1,2-dimethylhydrazine (DMH), which were found to induce NA in cells in the proliferative region of crypts 24 h after they were given to mice. Methylurea (MU) and benzo[e]pyrene (B[e]P), which are non-carcinogenic structural analogues of MNU and B[a]P, respectively, did not induce NA under similar conditions. Based on these results, the ability of an agent to induce NA in the small intestine appears to reflect of its oncogenic potential in that organ.