title: Genotoxic activities of 2-nitronaphthofurans and related molecules.
abstract: The genotoxic activities of 63, 2-nitronaphthofurans and related molecules were examined using two bacterial short-term tests, the Salmonella mammalian microsome assay test or Mutatest, a mutagenesis assay, and/or the SOS Chromotest, an assay for induction of an SOS function in Escherichia coli. Seven compounds were also investigated in the Chinese hamster ovary cells/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) test, a mammalian gene mutation assay. Our main conclusions are the following: (a) Simple empirical rules relating structure to mutagenic activity in the Mutatest can be derived for some of the compounds. In particular, they account for the extremely high Mutagenic Potency of 7-methoxy-1-methyl-2-nitronaphtho[2,1-b]furan (R7372), approximately 2 X 10(6) mutants/nmol on strain TA100. (b) There is a good quantitative correlation between the Mutagenic Potency in the Salmonella/mammalian microsomes assay and the SOS-inducing potency in the SOS Chromotest. This, and previous evidence, suggests strongly that the 2-nitronaphthofurans derivatives are essentially recA and thus probably umuDC-dependent mutagens. (c) Four out of seven compounds tested in the CHO/HGPRT assay gave responses correlated with the bacterial responses. One of them, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), is among, or is, the strongest mutagen described for mammalian cells. We briefly discuss the practical and theoretical implications of these results.
authors.affiliation: Unité de Programmation Moléculaire et Toxicologie Génétique, CNRS LA271, INSERM U163, Institut Pasteur, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Arnaise
authors.forename: H
authors.initials: H
authors.lastname: Boeuf
authors.forename: J P
authors.initials: JP
authors.lastname: Buisson
authors.forename: N
authors.initials: N
authors.lastname: Cantat
authors.forename: P
authors.initials: P
authors.lastname: Demerseman
authors.forename: J
authors.initials: J
authors.lastname: Einhorn
authors.forename: G
authors.initials: G
authors.lastname: Lamotte
authors.forename: M
authors.initials: M
authors.lastname: Lemelin
authors.forename: P A
authors.initials: PA
authors.lastname: Brimer
authors.forename: S W
authors.initials: SW
authors.lastname: Perdue
mesh_terms: D055598:Chemical Phenomena; D002621:Chemistry; D009152:Mutagenicity Tests; D009153:Mutagens; D009581:Nitrofurans / Q000009:adverse effects*; D013329:Structure-Activity Relationship
chemical_list: D009153:Mutagens; D009581:Nitrofurans