Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC# 101)

• Published in: Biochemical and biophysical research communications Vol. 344; no. 1; pp. 129 - 133
• Main Authors: McGraw, Joseph E., Waller, Donald P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-05-2006
• Subjects: 2,2′,4′,5,5′- Pentachlorobiphenyl; 4-Hydroxy-2,2′,4′,5,5′-pentachlorobiphenyl; 4-Hydroxy-PCB 101; Aryl Hydrocarbon Hydroxylases - analysis; Aryl Hydrocarbon Hydroxylases - metabolism; CYP 2A6; CYP 450; Cytochrome P-450 CYP2A6; Cytochrome P-450 Enzyme System - analysis; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - metabolism; Environmental Pollutants - metabolism; Humans; Isoenzymes - analysis; Isoenzymes - metabolism; Metabolism; Microsomes, Liver - enzymology; Mixed Function Oxygenases - analysis; Mixed Function Oxygenases - metabolism; PCB 101; PCBs; Polychlorinated biphenyls; Polychlorinated Biphenyls - metabolism; Recombinant human enzymes; Recombinant Proteins - metabolism; PCBs; Recombinant human enzymes; 4-Hydroxy-2,2′,4′,5,5′-pentachlorobiphenyl; CYP 2A6; Polychlorinated biphenyls; PCB 101; 4-Hydroxy-PCB 101; Metabolism; 2,2′,4′,5,5′- Pentachlorobiphenyl; CYP 450
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.03.122

Polychlorinated biphenyl IUPAC# 101-PCB 101 (chlorination pattern-2,2′,4′,5,5′) is a common, persistent non-coplanar PCB congener found in the ambient environment but information related to its metabolism in humans is lacking. Previous studies indicate PCB 101 is rapidly metabolized in mammals through CYP 2B and 3A family enzymes. Recently, PCB metabolism through a 2A family isoform in hamsters was also reported. To specifically identify the human CYP 450 isoforms responsible for PCB 101 metabolism, we compared human microsome metabolism to metabolism using several specific recombinant human CYP isoforms. These data characterized selective and extensive metabolism by human CYP 2A6. The product formed was the 4-hydroxy-PCB 101 metabolite (4-hydroxy-2,2′,4′,5,5′) and was the only major metabolite observed in the recombinant and human microsome investigation. This is important information for predicting human specific toxicokinetics of PCBs.