Influence of polyhalogenated aromatic hydrocarbons on the induction, activity, and stabilization of cytochrome P450

Thesis/Dissertation · Thu Jan 01 04:00:00 EST 1987

OSTI ID:6922094

Voorman, R

In the course of experiments evaluating the metabolism of polybrominated biphenyls by cytochrome P450 isozymes induced by 3,4,5,3',4',5'-hexabromobiphenyl (HBB), it was discovered that the inducer remained closely associated with cytochrome P450d. Subsequent purification of cytochromes from HBB treated rates revealed a 0.5:1 association of HBB to cytochrome P450d but virtually none with cytochrome P450c or cytochrome b5. Immunochemical quantitation of cytochrome P450d in the same microsomes yielded a ratio of P450d:HBB that approached unity. Measurement of cytochrome P450d estradiol 2-hydroxylase indicated non-competitive or mixed type inhibition caused by HBB at a concentration of 10-1000 nM. Inhibition was specific to cytochrome P450d since estradiol 2-hydroxylase catalyzed by cytochrome P450h was unaffected by HBB. The ability of HCB and isosafrole to stabilize cytochrome P450d, and thus indirectly influence regulation of the enzyme, was evaluated by treating rats with a dose of TCDD sufficient to produce maximum induction of cytochromes P450c and P450d via the Ah receptor, yet insufficient to bind to the enzyme. Subsequent treatment of these animals with HCB or isosafrole and a radiolabeled amino acid, revealed a significant increase in cytochrome P450d specific content relative to cytochrome P450c and significant retention of the radiolabel in P450d relative to rats treated only with TCDD.

• Research Organization: Michigan State Univ., East Lansing (USA)
• OSTI ID: 6922094
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CYTOCHROMES
DIOXIN
ENZYME ACTIVITY
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXYLASES
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
LIGANDS
MAMMALS
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
PIGMENTS
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
RADIOISOTOPES
RATS
RODENTS
TRACER TECHNIQUES
VERTEBRATES