Genotoxic activities of 2-nitronaphthofurans and related molecules.
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.
Arnaise
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S
Unité de Programmation Moléculaire et Toxicologie Génétique, CNRS LA271, INSERM U163, Institut Pasteur, Paris, France.
Boeuf
H
H
Buisson
J P
JP
Cantat
N
N
Demerseman
P
P
Einhorn
J
J
Lamotte
G
G
Lemelin
M
M
Brimer
P A
PA
Perdue
S W
SW
D055598:Chemical Phenomena; D002621:Chemistry; D009152:Mutagenicity Tests; D009153:Mutagens; D009581:Nitrofurans / Q000009:adverse effects*; D013329:Structure-Activity Relationship
D009153:Mutagens; D009581:Nitrofurans