Abstract
We reported previously that the dog is a unique species which can metabolize 2, 4, 5, 2', 4', 5'-hexachlorobiphenyl (HCB) by unusual mechanism via 2,3-arene oxide intermediate formation. 2, 4, 5, 2', 4', 5'-HCB is known as one of the PCB congeners showing the highest concentration in the blood of Yusho patients at present. Therefore, further investigation on the mechanism of biotransformation of PCB in the dog is very useful to obtain informations about metabolic fates of persistent congeners in the bodies of Yusho patients. In the present study, we examined in vivo metabolic pathways of 2, 4, 6, 2', 4', 6'-HCB in a dog, and also a role of cytochrome P-450 isozymes in its metabolism. In these experiments, three major metabolites were found in feces of the dog. These were identified to be 3-hydroxy-2, 4, 6, 2', 4', 6'-HCB (M-1), 4-hydroxy-2, 6, 2', 4', 6'-pentachlorobiphenyl (M-2) and 3, 4-dihydroxy-2, 6, 2', 4', 6'-PenCB (M-3), which were previously identified as the major metabolites in vitro. 4-Hydroxy-2, 3, 6, 2', 4', 6'-HCB has also been isolated as a metabolite in vitro, but not detected in this in vivo study. In conclusion, the present in vivo study supported the previous in vitro results that the dog metabolizes this congener at least two mechanisms including direct hydroxylation and arene oxide formation. It was also indicated that cytochrome P-450 isozymes responsible for metabolism of this congener may be in part different from those catalyzing the 2, 4, 5, 2', 4', 5'-HCB metabolism.
| Original language | English |
|---|---|
| Pages (from-to) | 181-188 |
| Number of pages | 8 |
| Journal | Fukuoka Acta Medica |
| Volume | 84 |
| Issue number | 5 |
| Publication status | Published - May 1993 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
Metabolism in vivo of 2, 4, 6, 2', 4', 6'-hexachlorobiphenyl in dog and partial characterization of cytochrome P-450 isozyme responsible for biotransformation of the congener. / Ariyoshi, Noritaka; Shigeto, M.; Oguri, K.; Yoshimura, H.
In: Fukuoka Acta Medica, Vol. 84, No. 5, 05.1993, p. 181-188.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metabolism in vivo of 2, 4, 6, 2', 4', 6'-hexachlorobiphenyl in dog and partial characterization of cytochrome P-450 isozyme responsible for biotransformation of the congener
AU - Ariyoshi, Noritaka
AU - Shigeto, M.
AU - Oguri, K.
AU - Yoshimura, H.
PY - 1993/5
Y1 - 1993/5
N2 - We reported previously that the dog is a unique species which can metabolize 2, 4, 5, 2', 4', 5'-hexachlorobiphenyl (HCB) by unusual mechanism via 2,3-arene oxide intermediate formation. 2, 4, 5, 2', 4', 5'-HCB is known as one of the PCB congeners showing the highest concentration in the blood of Yusho patients at present. Therefore, further investigation on the mechanism of biotransformation of PCB in the dog is very useful to obtain informations about metabolic fates of persistent congeners in the bodies of Yusho patients. In the present study, we examined in vivo metabolic pathways of 2, 4, 6, 2', 4', 6'-HCB in a dog, and also a role of cytochrome P-450 isozymes in its metabolism. In these experiments, three major metabolites were found in feces of the dog. These were identified to be 3-hydroxy-2, 4, 6, 2', 4', 6'-HCB (M-1), 4-hydroxy-2, 6, 2', 4', 6'-pentachlorobiphenyl (M-2) and 3, 4-dihydroxy-2, 6, 2', 4', 6'-PenCB (M-3), which were previously identified as the major metabolites in vitro. 4-Hydroxy-2, 3, 6, 2', 4', 6'-HCB has also been isolated as a metabolite in vitro, but not detected in this in vivo study. In conclusion, the present in vivo study supported the previous in vitro results that the dog metabolizes this congener at least two mechanisms including direct hydroxylation and arene oxide formation. It was also indicated that cytochrome P-450 isozymes responsible for metabolism of this congener may be in part different from those catalyzing the 2, 4, 5, 2', 4', 5'-HCB metabolism.
AB - We reported previously that the dog is a unique species which can metabolize 2, 4, 5, 2', 4', 5'-hexachlorobiphenyl (HCB) by unusual mechanism via 2,3-arene oxide intermediate formation. 2, 4, 5, 2', 4', 5'-HCB is known as one of the PCB congeners showing the highest concentration in the blood of Yusho patients at present. Therefore, further investigation on the mechanism of biotransformation of PCB in the dog is very useful to obtain informations about metabolic fates of persistent congeners in the bodies of Yusho patients. In the present study, we examined in vivo metabolic pathways of 2, 4, 6, 2', 4', 6'-HCB in a dog, and also a role of cytochrome P-450 isozymes in its metabolism. In these experiments, three major metabolites were found in feces of the dog. These were identified to be 3-hydroxy-2, 4, 6, 2', 4', 6'-HCB (M-1), 4-hydroxy-2, 6, 2', 4', 6'-pentachlorobiphenyl (M-2) and 3, 4-dihydroxy-2, 6, 2', 4', 6'-PenCB (M-3), which were previously identified as the major metabolites in vitro. 4-Hydroxy-2, 3, 6, 2', 4', 6'-HCB has also been isolated as a metabolite in vitro, but not detected in this in vivo study. In conclusion, the present in vivo study supported the previous in vitro results that the dog metabolizes this congener at least two mechanisms including direct hydroxylation and arene oxide formation. It was also indicated that cytochrome P-450 isozymes responsible for metabolism of this congener may be in part different from those catalyzing the 2, 4, 5, 2', 4', 5'-HCB metabolism.
UR - http://www.scopus.com/inward/record.url?scp=0027598404&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027598404&partnerID=8YFLogxK
M3 - Article
VL - 84
SP - 181
EP - 188
JO - Fukuoka Acta Medica
JF - Fukuoka Acta Medica
SN - 0016-254X
IS - 5
ER -