Mutagenicity of nitro derivatives produced by exposure of dibenzofuran to nitrogen oxides.
Dibenzofuran (DF) was reacted with various concentrations of nitrogen oxides (NOx) under light irradiation. The mutagenicities of the reaction mixtures were tested using Salmonella typhimurium strains TA98, TA100, TA98NR and TA98/1,8-DNP6 in the presence or absence of a mammalian metabolic activation system (S9 mix). DF-Nox (molar ratios 1:3, 1:6 and 1:18) reaction mixtures exhibited mutagenic potency in strain TA98 without S9 mix, and their direct-acting mutagenicity was reduced in strains TA98NR and TA98/1,8-DNP6. Four mononitrodibenzofurans and 2 dinitrodibenzofurans, i.e., 1-nitrodibenzofuran (NDF), 2-NDF, 3-NDF, 4-NDF, 2,7-dinitrodibenzofuran (DNDF) and 2,8-DNDF, were identified with authentic samples in the DF-NOx (1:18) reaction mixture by HPLC cochromatography and a gas chromatography/mass spectrometry study. The order of mutagenicity of nitrodibenzofurans in strain TA98 without S9 mix was as follows: 2,7-DNDF greater than 2,8-DNDF greater than 3-NDF greater than 2-NDF greater than 4-NDF greater than 1-NDF. The mutagenic potency of 2,7-DNDF in strains TA98 and TA100 was enhanced by the addition of S9 mix. Since these nitrodibenzofurans were less mutagenic in strains TA98NR and TA98/1,8-DNP6 than in strain TA98 without S9 mix, it was presumed that their mutagenicity was dependent on their activation by the 'classical' bacterial nitroreductase and/or transacetylase, which are absent in strains TA98NR and TA98/1,8-DNP6 but present in strain TA98, respectively. 3-NDF and 4-NDF were mutagenic in strain TA100 without S9 mix. 2-NDF and 3-NDF were determined as corresponding amino derivatives in DF-NOx (1:3), (1:6) and (1:18) reaction mixtures. They contributed about 30-65% of the direct-acting mutagenicity of reaction mixtures in strain TA98.
Watanabe
T
T
Kyoto Pharmaceutical University, Japan.
Hirayama
T
T
D000818:Animals; D001572:Benzofurans / Q000737:chemistry*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D008027:Light; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D001572:Benzofurans; D009153:Mutagens; D009574:Nitro Compounds; D009589:Nitrogen Oxides; C023614:dibenzofuran