Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human cells

Biochemical Pharmacology
W B ParkerL L Bennett

Abstract

Activation of purine nucleoside analogs by Escherichia coli purine nucleoside phosphorylase (PNP) is being evaluated as a suicide gene therapy strategy for the treatment of cancer. Because the mechanisms of action of two toxic purine bases, 6-methylpurine (MeP) and 2-fluoroadenine (F-Ade), that are generated by this approach are poorly understood, mechanistic studies were initiated to learn how these compounds differ from agents that are being used currently. The concentration of F-Ade, MeP, or 5-fluorouracil required to inhibit CEM cell growth by 50% after a 4-hr incubation was 0.15, 9, or 120 microM, respectively. F-Ade and MeP were also toxic to quiescent MRC-5, CEM, and Balb 3T3 cells. Treatment of CEM, MRC-5, or Balb 3T3 cells with either F-Ade or MeP resulted in the inhibition of protein, RNA, and DNA syntheses. CEM cells converted F-Ade and MeP to F-ATP and MeP-ribonucleoside triphosphate (MeP-R-TP), respectively. The half-life for disappearance of HeP-ribonucleoside triphosphate from CEM cells was approximately 48 hr, whereas the half-lives of F-ATP and ATP were approximately 5 hr. Both MeP and F-Ade were incorporated into the RNA and DNA of CEM cells. These studies indicated that the mechanisms of action of F-Ade and M...Continue Reading

References

Dec 14, 1979·Biochemical and Biophysical Research Communications·T P ZimmermanG S Duncan
Jan 1, 1990·Pharmacology & Therapeutics·W B Parker, Y C Cheng
Aug 1, 1971·Nature: New Biology·A HershkoG M Tomkins
Nov 1, 1970·The Journal of protozoology·D L HillP W Allan
Sep 1, 1965·Archives of Biochemistry and Biophysics·H T ShigeuraM L Meloni
May 31, 1983·Biochemical and Biophysical Research Communications·V I Avramis, W Plunkett
Aug 1, 1994·Pharmacology & Therapeutics·C A Mullen
May 1, 1994·Trends in Genetics : TIG·K W Culver, R M Blaese
Oct 10, 1997·Human Gene Therapy·W B ParkerE J Sorscher
Jun 1, 1960·Biochemical Pharmacology·V C DEWEYG W KIDDER
May 18, 1964·Biochimica Et Biophysica Acta·L L BENNETTC T WARD
Sep 1, 1964·Biochemical Pharmacology·L L BENNETT, D SMITHERS

❮ Previous
Next ❯

Citations

Dec 23, 2003·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Tae Hyun ChoiSang Moo Lim
May 5, 2001·Pharmacology & Therapeutics·A BzowskaD Shugar
Jun 28, 2011·Cancer Gene Therapy·S BossowG Ungerechts
May 26, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tanner S MiestRoberto Cattaneo
Oct 19, 2007·Nature Reviews. Cancer·Douglas HedleyCaroline Springer
Aug 23, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Guy UngerechtsRoberto Cattaneo
Jun 8, 2000·Nucleosides, Nucleotides & Nucleic Acids·A E HassanJ A Secrist
Apr 12, 2008·BMC Cancer·Jochen StritzkerWerner Goebel
Dec 5, 2009·Journal of Experimental & Clinical Cancer Research : CR·Sepideh AfsharSherie L Morrison
Dec 3, 2013·Nature Reviews. Microbiology·Tanner S Miest, Roberto Cattaneo
Jan 23, 2010·Experimental Parasitology·Sonali MehrotraHemalatha Balaram
Jun 9, 2009·Antiviral Research·Dong-Hoon ChungColleen B Jonsson
Nov 23, 2010·Expert Review of Vaccines·Patrycja J Lech, Stephen J Russell
Jul 10, 2014·The AAPS Journal·Irene GiangGregory M K Poon
Apr 23, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E L RosenthalE J Sorscher
Feb 20, 2007·Molecular Aspects of Medicine·Daniel PortsmouthMatthias Renner
Nov 12, 2003·Nucleosides, Nucleotides & Nucleic Acids·Song YeKenneth L Kirk
Apr 19, 2002·Cancer Gene Therapy·Rosetta Martiniello-WilksPamela J Russell
Sep 13, 2018·Experimental Biology and Medicine·Stephen J JonesPaul A Beales
Jan 10, 2002·Microbiology·Chih-Kuang ChenWilliam B Parker
Feb 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·Vijayakrishna K GadiEric J Sorscher
Sep 25, 2019·Cancers·Marcella CamiciMaria Grazia Tozzi

❮ 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.