Evidence that the antitumor agent hydroxyurea enters mammalian cells by a diffusion mechanism

Biochemical and Biophysical Research Communications
J S MorganJ A Wright

Abstract

Very little information is available about the process responsible for the uptake of the antitumor agent hydroxyurea by mammalian cells. Therefore we have investigated the transport of hydroxy[14C]-urea into Chinese hamster ovary cells. Using a convenient and reproducible 2 min. assay we found that hydroxyurea was taken up in a linear nonsaturable fashion between 0.01 mM and 100 mM drug. The Km for hydroxyurea uptake was essentially zero and the Vmax appeared to be infinite, suggesting a diffusion mechanism. The observation that intracellular drug concentrations were consistently less than medium concentrations indicated that uptake was not an active process. Experiments performed with the metabolic inhibitor sodium azide, and investigations at different assay temperatures also gave results consistent with a mechanism of drug diffusion. In total, the results obtained in this study are in agreement with the proposal that hydroxyurea enters the cell primarily by a process of diffusion. These observations provide a more complete understanding of the mode of action of this widely used drug.

Citations

Feb 26, 2000·European Journal of Pharmacology·J F GoossensC Bailly
Oct 13, 2009·Fundamental & Clinical Pharmacology·Hind SassiAnne Hulin
May 1, 1989·Biopharmaceutics & Drug Disposition·M MerinoJ M Plá-Delfina
Jan 13, 1998·Molecular Pharmacology·J JiangR P Mason

❮ 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.