In vitro and in vivo studies on the metabolism of 1,3-diaminobenzene: Comparison of metabolites formed by the perfused rat liver, primary rat hepatocyte cultures, hepatic rat microsomes and the whole rat.
The metabolism of the aromatic amine 1,3-diaminobenzene (MPD) was studied in vitro by use of the perfused rat liver, primary rat hepatocyte cultures and hepatic rat microsomes. The metabolites formed were compared with urinary metabolites excreted by the rat in vivo. Metabolites of [(14)C]MPD excreted by the perfused liver were found to be identical with urinary excreted metabolites in vivo, three of which were found to correlate with the N-acetylated derivatives N,N'-diacetyl-1,3-diaminobenzene, N,N'-diacetyl-2,4-diaminophenol and N-acetyl-1,3-diaminobenzene. Also, the primary hepatocyte cultures formed the metabolites found in the urine. However, several other metabolites, including some glucuronic acid conjugates, could be detected in the culture medium. In contrast to the perfused liver and the primary hepatocyte cultures, a reconstituted microsomal system was unable to form any of the metabolites formed by the other in vitro models and in vivo. The results show that in addition to the metabolites that can be detected in the urine in vivo, several other derivatives, including glucuronic acid conjugates of MPD, are formed by the rat liver. The results suggest that primary rat hepatocyte cultures are the preferred model system in metabolic studies in vitro and will constitute useful supplements to metabolic studies performed in the rat in vivo.
Bisgaard
H C
HC
Institute of Toxicology, National Food Agency, 19 Mørkhøj Bygade, DK-2860 Søborg, Denmark.
Lam
H R
HR