Learn More
Gamma-glutamyltranspeptidase-positive hepatocyte foci were produced in female rats given a single dose of diethylnitrosamine neonatally after birth and, after weaning, a diet containing phenobarbitone for 30 wk. The nucleator method, a new stereological approach, provided an efficient, unbiased estimate of mean cell volume in focal lesions and extrafocal(More)
Acyl-Coenzyme A thioesters of the hypolipidaemic and cancerinogenic peroxisome proliferators clofibric acid, nafenopin, ciprofibrate, bezafibrate and tibric acid were found to greatly increase the activity of rat brain protein kinase C. Maximal activation required the simultaneous presence of Ca+2, phosphatidylserine and diolein, thus differentiating their(More)
Further understanding of the mechanism by which peroxisome proliferators induce liver tumours is essential to assessing the risks of such compounds to exposed humans. To this end the effects of nafenopin upon the liver have been investigated. Nafenopin was shown to induce certain drug metabolising enzymes, but sub-cellular fractions from induced animals did(More)
Using trans-stilbene oxide and styrene oxide as substrates, epoxide hydrolase activities were measured in cytosolic and microsomal fractions from liver, kidney, heart, lung and testis of male DBA/2 mice. The activities towards these two substrates are remarkably organ specific: trans-stilbene oxide was most effectively hydrolyzed in subcellular fractions(More)
Using trans-stilbene oxide as substrate, the subcellular distribution of epoxide hydrolase was investigated in livers from DBA/2 mice. The highest specific activities were found in cytosolic and light mitochondrial fractions. Isopycnic subfractionation of the light mitochondrial fraction showed that the organelle-bound trans-stilbene oxide hydrolase is(More)
In a variety of biological systems, the cellular response to an extracellular stimulus is mediated by a complex cascade of biochemical signals transduced from the cellular membrane to the specific part(s) of the cell where the response(s) occur(s). The signal transduction pathways do form a matrix of several reactions involving increased intracellular free(More)
The effect of nafenopin upon primary cultures of adult rat hepatocytes has been investigated. Nafenopin treatment resulted in a proliferation of peroxisomes within the cultured cells. This proliferation was the result of an increase in both the number and size of the peroxisomes. Nafenopin treatment also caused an increased level of thymidine incorporation(More)
Peroxisome proliferation in rodents is associated with hepatocarcinogenicity. This association has led to increased interest in the phenomenon and to the search for in vitro tests to detect peroxisome proliferators and to study the mechanisms by which proliferation occurs. Primary cultures of adult rat hepatocytes provide such a system: peroxisomal enzymes,(More)
The repeated oral administration of nafenopin, a hypolipidaemic compound, at a dose of 100 mg/kg to male C57BL/6, DBA/2, Balb c and C3H mice caused an increase in the specific activity of liver cytosolic epoxide hydrolase, the activity of microsomal epoxide hydrolase was also increased in all except the C3H mice. The dose dependence and the specificity of(More)