Mutagenic properties of a nitrofuran, 7-methoxy-2-nitronaphtho[2,1-b]furan(R7000), in lacI transgenic mice

The in vivo mutagenic properties of a 5-nitrofuran, the 7-methoxy-2-nitrana phtho[2,1-b]furan (R7000), already well known in bacteria, was evaluated in lad transgenic mice (Big Blue). The mutation frequency was determined in v arious organs of i.p. - treated mice and the nature of induced mutations wa s determined for the target organs in which mutation induction was signific ant. It was found that R7000 is mutagenic in mice, although, on the basis o f the number of induced mutants per unit mass in comparison with other know n mutagenic chemicals, R7000 appears to be considerably less mutagenic in m ice than in bacteria. The most affected organs, small intestine, caecum and colon organs belong to the digestive apparatus. The distribution of R7000- induced mutations in the lad gene recovered from small intestine of transge nic mice was very similar to that which had been found in E. coli. The diff erence between mouse and E, coli in the R7000 induced mutational spectra ar e mainly in the proportion of single base frameshifts versus base substitut ions. Since R7000 induced mutations seemed to arise in the population of st em cells and that the stem cells are important for carcinogenesis, our resu lts are compatible with a possible carcinogenic effect of R7000 and other n itrofurans. (C) 2000 Elsevier Science B.V. All rights reserved.