Evaluation of the genotoxic activity of 2-nitroanthrafurans.
We measured the genotoxic activities in two bacterial tests, the Salmonella/histidine assay (a reverse mutation assay) and the SOS chromotest (an assay for SOS induction in E. coli), of three 2-nitroanthrafurans: 2-nitroanthra[1,2-b]furan (R-7688), the isomeric compound 2-nitroanthra[2,1-b]furan (R-7686) and its 8-methoxylated derivative (R-7707). Their genotoxic activities were compared to that of 7-methoxy-2-nitronaphtho[2,1-b]furan (R-7000) which has been studied in previous works (Arnaise et al., 1986). We found that: (1) for all three 2-nitroanthrafurans, as generally observed for other 2-nitrofuran derivatives, the responses were correlated in the 2 tests and were decreased in the presence of an 'activating mixture' and in nitroreductase-deficient strains; (2) in contrast to what is usually observed with other 2-nitrofuran derivatives for which methoxylation increases genotoxic activity, the genotoxic activity of the methoxylated 2-nitroanthrafuran (R-7707) was comparable and may be even lower than that of the unsubstituted 2-nitroanthrafuran (R-7686); (3) the addition of a third ring that leads from 2-nitronaphthofurans to 2-nitroanthrafurans increased slightly the genotoxic activity of these compounds; (4) compounds with the oxygen heteroatom outside the 'bay region', R-7686 and R-7707, gave higher responses than their isomers with the oxygen heteroatom within the 'bay region', R-7688.
Quillardet
P
P
Unit of Molecular Programming and Genetic Toxicology, CNRS UA 271, Institut Pasteur, Paris, France.
Bilger
C
C
Demerseman
P
P
Royer
R
R
Hofnung
M
M
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D001711:Biotransformation; D004260:DNA Repair / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009581:Nitrofurans / Q000494:pharmacology*; D009601:Nitroreductases / Q000378:metabolism; D051381:Rats; D013014:SOS Response, Genetics / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000873:Anthracenes; D001426:Bacterial Proteins; D009581:Nitrofurans; C030911:2-nitro-7-methoxynaphtho(2-1b)furan; D009601:Nitroreductases