Mode of action and human relevance of THF-induced mouse liver tumors

Toxicology Letters
Christopher J ChoiRalph J Parod

Abstract

In a National Toxicology Program (NTP) bioassay, inhalation of tetrahydrofuran (THF) induced liver tumors in female B6C3F1 mice but not in male mice or rats of either sex. Since THF is not genotoxic, the NTP concluded this carcinogenic activity was likely mediated via non-genotoxic modes of action (MOA). Based on evidence that THF and phenobarbital share a similar MOA, female Car/Pxr knock-out mice were orally exposed to THF to evaluate the potential role of CAR activation in the MOA for THF-induced liver tumors. Because data from this oral study with Car/Pxr knock-out mice (C57Bl/6) and the inhalation studies with wild type mice (B6C3F1) reported by NTP and others were derived from different strains, oral studies with wild type B6C3F1 and C57Bl/6 mice were conducted to ensure THF responses in both strains were comparable. As seen in inhalation studies with THF, oral exposure of wild type female mice to a maximum tolerated dose of THF increased total P450 content, CAR-related P450 activities, and hepatocyte proliferation; these effects were not observed in Car/Pxr knock-out female mice. This finding supports the hypothesis THF-induced carcinogenicity is likely mediated via CAR activation that has limited, if any, relevance to h...Continue Reading

References

Jun 13, 1979·Biochemical and Biophysical Research Communications·M BronfmanF Leighton
Feb 4, 1998·Biochemical Pharmacology·H ZaherF J Gonzalez
Oct 22, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·A O GamerB van Ravenzwaay
Jun 17, 2003·Carcinogenesis·Giovanna M Ledda-ColumbanoAmedeo Columbano
Oct 14, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michael P HolsappleYvonne P Dragan
Jan 30, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tomoya YamadaHideo Kaneko
Nov 10, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Curtis J OmiecinskiJeffrey M Peters
Feb 15, 2011·Regulatory Toxicology and Pharmacology : RTP·Penelope A Fenner-CrispRaymond M David
Mar 16, 2013·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Carlo La Vecchia, Eva Negri
May 17, 2014·Critical Reviews in Toxicology·Matthew J LeBaronReza J Rasoulpour

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

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.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

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.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Toxicological Sciences : an Official Journal of the Society of Toxicology
R S ChhabraR A Renne
Regulatory Toxicology and Pharmacology : RTP
George CruzanMichael G Thomas
© 2022 Meta ULC. All rights reserved