Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli

Toxicology Letters
K TanakaK Doi


Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis.


Feb 28, 1979·Biochemical and Biophysical Research Communications·K D BrownE Rozengurt
Nov 1, 1991·Proceedings of the Society for Experimental Biology and Medicine·B E Butterworth, T L Goldsworthy
Aug 31, 1990·Science·S M Cohen, L B Ellwein
Mar 13, 1986·Biochemical and Biophysical Research Communications·D L HwangB I Carr
Dec 3, 1981·The New England Journal of Medicine·E Farber

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Separation Anxiety

Separation anxiety is a type of anxiety disorder that involves excessive distress and anxiety with separation. This may include separation from places or people to which they have a strong emotional connection with. It often affects children more than adults. Here is the latest research on separation anxiety.

KIF1A Associated Neurological Disorder

KIF1A associated neurological disorder (KAND) is a rare neurodegenerative condition caused by mutations in the KIF1A gene. KAND may present with a wide range and severity of symptoms including stiff or weak leg muscles, low muscle tone, a lack of muscle coordination and balance, and intellectual disability. Find the latest research on KAND here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.