Effect of some peroxisome proliferators on transforming growth factor-beta 1 gene expression and insulin-like growth factor II/mannose-6-phosphate receptor gene expression in rat liver.
Male Sprague-Dawley rats were given daily oral doses of either corn oil (control), 80 mg/kg nafenopin (NAF), 50 mg/kg methylclofenapate (MCP), 50 mg/kg Wy-14,643 (WY) or 250 mg/kg clofibric acid (CA) for 7 days. All four compounds increased relative liver weight and produced hepatic peroxisome proliferation as assessed by induction of both peroxisomal (palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylase) fatty acid oxidising enzyme activities. RNA was extracted from liver samples and analysed for expression of transforming growth factor-beta 1 (TGF-beta 1) and the insulin-like growth factor II/mannose-6-phosphate (IGFII/Man6P) receptor (which may be involved in transporting latent TGF-beta 1 into hepatocytes). TGF-beta 1 mRNA levels were increased to 151-178% of control by all four compounds, whereas NAF, MCP and WY, but not CA, increased IGFII/Man6P receptor mRNA levels to 195-209% of control. The induction of TGF-beta 1 and IGFII/Man6P receptor expression by short term treatment with peroxisome proliferators may represent an adaptive response to limit the initial hyperplastic effects of such compounds.
Rumsby
P C
PC
BIBRA Toxicology International, Carshalton, Surrey, UK.
Davies
M J
MJ
Price
R J
RJ
Lake
B G
BG
D000818:Animals; D002992:Clofenapate / Q000633:toxicity; D002995:Clofibric Acid / Q000633:toxicity; D003314:Corn Oil / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D009255:Nafenopin / Q000633:toxicity; D011743:Pyrimidines / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D011743:Pyrimidines; D017527:Receptor, IGF Type 2; D016212:Transforming Growth Factor beta; D009255:Nafenopin; D002992:Clofenapate; D002995:Clofibric Acid; D003314:Corn Oil; C006253:pirinixic acid