Microphotometric analysis of cytochrome P-450 in periportal, midzonal, and perivenular hepatocytes of mice treated with phenobarbital.
To obtain detailed information on the increase of cytochrome P-450 (P-450) content in periportal, midzonal, and perivenular hepatocytes after phenobarbital (PB) administration, and to study the mechanism of increased P-450 in the endoplasmic reticulum (ER), we estimated microphotometrically the P-450 content and morphometrically the area of ER in hepatocytes of three zones from mice injected with 35, 50, 100, or 150 mg/kg of PB for 3 days. The amount of P-450 per unit cytoplasmic volume and the number of P-450 molecules per unit ER area (P-450 number) were increased by injection of 50, 100, or 150 mg/kg, and the ER area per unit cytoplasmic volume was increased by injection of 100 or 150 mg/kg, in hepatocytes from all three zones. Thus, the amount of P-450 in hepatocytes appeared in general to increase multiplicatively by simultaneous increases in both the P-450 number and the ER area. Furthermore, we could recognize two general types of relationship in the P-450 number and ER area between the patterns of change and the increasing doses: (a) increase in the P-450 number without ER proliferation (active type) in periportal and perivenular hepatocytes after injection of low doses; and (b) increase in ER proliferation without increase in the P-450 number (passive type) in hepatocytes of all three zones after injection of high doses.
Kanai
K
K
Department of Anatomy, Kansai Medical University, Osaka, Japan.
Watanabe
J
J
Kanamura
S
S
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D010634:Phenobarbital / Q000494:pharmacology*; D010783:Photometry / Q000379:methods*
D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital