Metabolic activation of nitrodibenzofurans by rat liver in Salmonella/mutagenicity test.
The effect of metabolic activation on the mutagenicity of nitrodibenzofurans (NDF) by rat liver S9 was evaluated with S. typhimurium tester strains. Except for 1-nitrodibenzofuran (NDF), five tested NDFs were mutagenic in strains TA98 and TA98/1,8-DNP6 without S9 mix but were not mutagenic in strain TA98NR. NDFs mutagenized strain TA98NR with S9 mix, and the NAD(P)H system plus 3-methylcholanthrene-induced S9 (3-MC-S9) was the most effective. The specificity of S9 enzyme(s) participating in the activation of NDFs was different from that of endogenous enzyme(s) in strain TA98, i.e., the order of mutagenic potency of NDFs in strain TA98 without S9 mix was 2,8- = 2,7-->3-->2-->4-->1-nitrated dibenzofuran and 2-NDF and 2,8-dinitrodibenzofuran (DNDF) were more mutagenic than 3-NDF and 2,7-DNDF, respectively, in strain TA98NR with S9 mix. The mutagenic potency of 2-NDF, 4-NDF, 2,7-DNDF and 2,8-DNDF in strain TA98NR with S9 mix was stronger than those in strain TA98 without S9 mix and the cytosolic fraction of the 3-MC-S9 accounted for more of the activation than the microsomal fraction. Studies with electron donors and inhibitors indicated that xanthine oxidase and/or NAD(P)H-quinone oxido-reductase (NQOR) participated in the activation of NDFs. The mutagenic potency of NDFs in strain TA98NR with S9 mix (3-MC-S9) was reflected in the induction of NQOR by pretreatment of rats with 3-MC.
Watanabe
T
T
Kyoto Pharmaceutical University, Japan.
Kaji
H
H
Kasai
T
T
Hirayama
T
T
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D016296:Mutagenesis; D009153:Mutagens / Q000378:metabolism*; D009574:Nitro Compounds / Q000378:metabolism; D011808:Quinone Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014969:Xanthine Oxidase / Q000378:metabolism
D001572:Benzofurans; D009153:Mutagens; D009574:Nitro Compounds; D014969:Xanthine Oxidase; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases