Induction of renal mixed function oxidases in the rat and mouse: correlation with ultrastructural changes in the proximal tubule.
Rats and mice were pretreated with beta-naphthoflavone (BNF) at 100 mg/kg/day, ip, for 4 days, or polybrominated biphenyl (PBB) as a single ip dose at 150 mg/kg, and the temporal changes in renal mixed function oxidase (MFO) activity and ultrastructural changes in the proximal tubule were examined. Rat renal cytochrome P-450 (P-450), ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase (EROD) were increased 5 days following the first dose of inducer. P-450 content and enzyme activity peaked on Day 5 to Day 10 and returned to control values by Day 15. BNF and PBB caused proliferation of smooth endoplasmic reticulum (SER) in only the S3 segment of the rat proximal tubule. Histologic analysis indicated that there was a close correlation between the temporal changes in renal MFO activity and proliferation of SER in the S3 segment of the proximal tubule. In contrast to the rat, mouse renal P-450 and ECOD were not induced by either BNF or PBB nor was there any significant proliferation of SER in any segment of the proximal tubule. Mouse renal EROD was slightly increased on Day 5 but not Day 10 or 15 by BNF; PBB had no effect. In addition to proliferation of SER, these inducers also caused proliferation of peroxisomes in the rat and mouse proximal tubule. These results demonstrate a temporal relationship between induction of rat renal MFOs and proliferation of SER in specific sections of the proximal tubule and thus suggest that induction of these renal enzymes may also be restricted to specific cell populations of the kidney. A species difference apparently exists since proliferation of SER was not observed in the mouse.
D000818:Animals; D001571:Benzoflavones / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D011075:Polybrominated Biphenyls / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D011075:Polybrominated Biphenyls; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases