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-nitronaphtho[2,1-b]furan (R7000), already well known in bacteria, was evaluated in lacI transgenic mice (Big Blue). The mutation frequency was determined in various organs of i.p. - treated mice and the nature of induced mutations was determined for the target organs in which mutation induction was significant. It was found that R7000 is mutagenic in mice, although, on the basis of the number of induced mutants per unit mass in comparison with other known mutagenic chemicals, R7000 appears to be considerably less mutagenic in mice 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 lacI gene recovered from small intestine of transgenic mice was very similar to that which had been found in E. coli. The difference between mouse and E. coli in the R7000 induced mutational spectra are mainly in the proportion of single base frameshifts versus base substitutions. Since R7000 induced mutations seemed to arise in the population of stem cells and that the stem cells are important for carcinogenesis, our results are compatible with a possible carcinogenic effect of R7000 and other nitrofurans.
Quillardet
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P
Unité de Programmation Moléculaire et Toxicologie Génétique, CNRS Ura 1444, Institut Pasteur, 25 rue du Dr Roux, 75724 Cedex 15, Paris, France.
Michel
V
V
Arrault
X
X
Hofnung
M
M
Touati
E
E
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009153:Mutagens / Q000633:toxicity*; D009581:Nitrofurans / Q000633:toxicity*; D012097:Repressor Proteins / Q000235:genetics*
D001426:Bacterial Proteins; D017931:DNA Primers; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D009153:Mutagens; D009581:Nitrofurans; D012097:Repressor Proteins; C030911:2-nitro-7-methoxynaphtho(2-1b)furan