Metabolism of 2-nitrofluorene, 2-aminofluorene and 2-acylaminofluorenes in rat and dog and the role of intestinal bacteria.
1. The in vivo metabolism of 2-nitrofluorene (NF), an environmental pollutant, and 2-aminofluorene (AF) and its acylated derivatives, 2-formylaminofluorene (FAF) and 2-acetylaminofluorene (AAF), was examined in rat and dog. 2. 7-Hydroxy-2-nitrofluorene, 5-hydroxy-2-nitrofluorene, AF, AAF, FAF, 7-hydroxy-2-aminofluorene, 5-hydroxy-2-aminofluorene, 7-hydroxy-2-acetylaminofluorene, 5-hydroxy-2-acetylaminofluorene, 7-hydroxy-2-formylaminofluorene and 5-hydroxy-2-formylaminofluorene were identified as urinary and faecal metabolites of NF in rat and dog. 3. AAF and its hydroxylated derivatives were detected as major metabolites of NF in rat, but FAF and its hydroxylated metabolites were mainly excreted in dog. 4. AF, AAF, FAF and their hydroxylated metabolites were also identified as urinary and faecal metabolites of AF, AAF or FAF in rat, suggesting that AAF and FAF are interconverted via AF. 5. Treatment of rat and dog with antibiotics significantly decreased the urinary and faecal excretion of AF and its derivatives after oral administration of NF, and partly decreased the excretion of acylated metabolites after an oral dose of AF. 6. The caecal contents of untreated rats and some species of intestinal bacteria exhibited nitro-reductase activity toward NF, and acylating activity toward AF, affording AAF and FAF.
Ueda
O
O
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
Kitamura
S
S
Kubo
R
R
Yano
Y
Y
Kanzaki
Y
Y
Fujimoto
T
T
Tatsumi
K
K
Ohta
S
S
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001419:Bacteria / Q000378:metabolism*; D002432:Cecum / Q000378:metabolism / Q000382:microbiology; D004285:Dogs; D004785:Environmental Pollutants / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009601:Nitroreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D004785:Environmental Pollutants; D005449:Fluorenes; C019499:2-nitrofluorene; C012177:2-aminofluorene; D015073:2-Acetylaminofluorene; D009601:Nitroreductases