Purification and characterization of the dog hepatic cytochrome P-450 isozyme(s) responsible for the metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5463701

Duignan, D B; Sipes, I G; Leonard, T B; Halpert, J R

Pretreatment of dogs and rats with phenobarbital (PB) enhances the in vitro metabolism of 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB); however, in control dog microsomes there is an approximately 5-fold greater rate of metabolism than that observed in PB-induced rat microsomes. At least two PB-induced isozymes of cytochrome P-450 are detected in dog microsomes, and by use of Octylamino-Sepharose. Hydroxylapatite, and DEAE-Sephacel column chromatography, one of these isozymes (which the authors call PBD-2) has been purified to >95%, as determined by SDS-PAGE. In a reconstituted system, PBD-2 can metabolize 245-HCB at a rate similar to that seen for PB-B, the major PB-induced isozyme in the rat. In addition, antibodies raised against PB-B cross-react with PBD-2, and the NH/sub 2/-terminal amino acid sequence of PBD-2 is nearly 70% homologous to that of PB-B. These results suggest that a cytochrome P-450 isozyme capable of metabolizing 245-HCB in the dog (PBD-2) is similar to PB-B. The importance of PBD-2 will be further elucidated by conducting inhibition studies with anti-PBD-2 antibodies in control and PB-induced dog microsomes.

• Research Organization: Univ. of Arizona, Tucson
• OSTI ID: 5463701
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHLORINATED AROMATIC HYDROCARBONS
METABOLISM
ISOENZYMES
PURIFICATION
AMINO ACID SEQUENCE
ANTIBODIES
CHROMATOGRAPHY
CYTOCHROMES
DOGS
LIVER
MICROSOMES
ANIMALS
AROMATICS
BODY
CELL CONSTITUENTS
DIGESTIVE SYSTEM
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
MAMMALS
MOLECULAR STRUCTURE
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
PIGMENTS
PROTEINS
SEPARATION PROCESSES
VERTEBRATES
550200* - Biochemistry