Induction of hepatic CYP1A in male F344/NCr rats by dietary exposure to Aroclor 1254: Examination of immunochemical, RNA, catalytic, and pharmacokinetic endpoints

Conference · Tue Dec 01 04:00:00 EST 1992 · Environmental Research; (United States)

OSTI ID:6713394

Nims, R W; Beebe, L E; Dragnev, K H; Lubet, R A ^[1]; Thomas, P E ^[2]; Fox, S D; Issaq, H J; Jones, C R ^[3]

---

1. National Cancer Inst., Frederick, MD (United States)
2. Rutgers-the State Univ., Piscataway, NJ (United States)
3. NCI-Frederick Cancer Research and Development Center, MD (United States)

Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9,000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased [approximately]4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP[sup +], benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and [approximately]10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. 46 refs., 6 figs., 4 tabs.

• OSTI ID: 6713394
• Report Number(s): CONF-9105413--; CNN: N01-CO-74102
• Conference Information: Journal Name: Environmental Research; (United States) Journal Volume: 59:2
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism &amp; Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MARKERS
CHLORINATED AROMATIC HYDROCARBONS
DOSE-RESPONSE RELATIONSHIPS
ENVIRONMENTAL EXPOSURE
HALOGENATED AROMATIC HYDROCARBONS
IMMUNE REACTIONS
INGESTION
INTAKE
KINETICS
LABORATORY ANIMALS
MAMMALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
POLYCHLORINATED BIPHENYLS
RATS
REACTION KINETICS
RODENTS
SENSITIVITY
TOXICITY
VERTEBRATES