Metabolism of 4-aminobiphenyl and 4-acetylaminobiphenyl in perfused guinea pig liver.
To obtain further knowledge of the metabolic fate of carcinogenic 4-aminobiphenyl (ABP) and 4-acetyl-aminobiphenyl (AABP) in intact guinea pig liver, we performed in situ liver perfusion using a recirculation method. Following a biexponential disappearance of ABP from the perfusate, not only AABP but also its secondary metabolites 4'-hydroxy AABP (4'-OH AABP) and 4-glycolylaminobiphenyl (GABP) appeared as the major metabolites. 4'-Hydroxy ABP (4'-OH ABP) was also detected in the perfusate as another predominant metabolite, while N-hydroxy ABP (N-OH ABP) as a minor one. Most of these metabolites, except for AABP and GABP, found in both perfusate and bile were conjugated with glucuronic acid. In addition, considerable amounts of all the metabolites were also detected in either unconjugated or conjugated form in a homogenate of the liver tissue after perfusion. When AABP was infused, an almost similar metabolic profile to that of ABP was obtained, but the amount of ABP was quite small and N-OH AABP rather than N-OH ABP was found. These results demonstrate that both ABP and AABP are rapidly metabolized by a combination of N-acetylation, C- and N-hydroxylations as well as glucuronidation in guinea pig liver.
Yoshihara
S
S
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Tatsumi
K
K
D000611:Aminobiphenyl Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D006168:Guinea Pigs; D006207:Half-Life; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion
D000611:Aminobiphenyl Compounds; C006757:4-biphenylamine; C020853:4-acetylaminobiphenyl