Regional induction of CYP1A1 in rat liver following treatment with mixtures of PCB 126 and PCB 153.
Liver enzyme induction has been shown previously to be regional with clear borders between induced and uninduced regions in vivo, and cells either fully induced or not induced in vitro. The current study examined this phenomenon in vivo by evaluating enzyme induction after exposure to PCB 126 and PCB 153 in female Fisher 344 (F344) and male Sprague-Dawley (SD) rats. IHC revealed a regional induction of CYP1A1 after exposure to PCB 126, apparent in the centrilobular region at lower doses and progressing to panlobular with higher doses. PCB 153 exposure induced CYP2B1/2 in the centrilobular region, which spread to the midzonal region as the dose increased, but never became panlobular even at the highest dosage tested. In rats treated with PCB 126 in combination with high doses of PCB 153, induction of CYP1A1 occurred preferentially in the periportal region, a reversal from the pattern seen with PCB 126 alone. This CYP1A1 induction pattern reversal is a unique example of complex biological interactions between coplanar (PCB 126) and noncoplanar (PCB 153) halogenated aromatic hydrocarbons.
Chubb
Laura S
LS
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523-1680, USA.
Andersen
Melvin E
ME
Broccardo
Carolyn J
CJ
Legare
Marie E
ME
Billings
Ruth E
RE
Dean
Charles E
CE
Hanneman
William H
WH
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000033:anatomy & histology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl