title: Mutagenic activity of dichloroethylamino derivatives of nitronaphthofuran and some nitrobenzofurans in the Salmonella/microsome assay.
abstract: The mutagenic activity of five dichloroethylamino 2-nitrobenzofuran derivatives and one dichloroethylamino 2-nitronaphthofuran derivative was analysed in the Salmonella/microsome assay. We investigated the influence of the position of the dichloroethylamino and/or the methoxy groups on the mutagenic activity of these nitro arenofurans in S. typhimurium strain TA100 and its variant TA100NR, deficient in nitroreductase. Without metabolic activation 7-[bis(2-chloroethyl)amino]-2-nitronaphtho[2,1-b]furan (1), 4-[bis(2-chloroethyl)amino]-7-methoxy-2-nitrobenzofuran (2), 7-[bis(2-chloroethyl)amino]-4-methoxy-2-nitrobenzofuran (5) and 6-[bis(2-chloroethyl)amino]-2-nitrobenzofuran (6) are mutagenic in TA100, while 4-[bis(2-chloroethyl)amino]-5-methoxy-2-nitrobenzofuran (4) is weakly mutagenic and 5-[bis(2-chloroethyl)-amino]-2-nitrobenzofuran (3) toxic. In the NR deficient strain compounds 1, 3 and 6 are strong mutagens and 4 is weakly positive. The two isomers 2 and 5 are negative in that strain. The naphthofuran derivative 1 is highly mutagenic in the absence of S9 mix in both strains considered, but less than R7000 (7). A decrease in the electronic polarity of compound 1 versus compound 7 according to the hypothesis developed by Royer et al. is a possible explanation. After exogenous metabolic activation by S9 mix all the compounds tested are highly mutagenic in both Salmonella strains. The position of the dichloroethylamino group and/or the presence of a methoxyl on the alpha-nitroarenofuran derivatives seem to modify the activity of bacterial as well as exogenous nitroreductases or other activating enzymes.
authors.affiliation: Institute of Hygiene and Epidemiology, Vrije Universiteit van Brussel, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Castelain
authors.forename: B
authors.initials: B
authors.lastname: Hendrickx
authors.forename: A
authors.initials: A
authors.lastname: Tromelin
authors.forename: P
authors.initials: P
authors.lastname: Demerseman
authors.forename: W
authors.initials: W
authors.lastname: Moens
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D001572:Benzofurans; D009153:Mutagens