Unbalanced Deoxyribonucleotide Synthesis Caused by Methotrexate
- 15 April 1972
- Vol. 2 (5806) , 140-142
- https://doi.org/10.1136/bmj.2.5806.140
Abstract
The effect of methotrexate on the free intracellular pools of thymidylate triphosphate (dTTP) and deoxyadenosine triphosphate (dATP) in normal human phytohaemagglutinin-transformed lymphocytes has been studied. Methotrexate caused a fall in the dTTP pool ranging from 38% to 88% and a rise in the dATP pool ranging from 24% to 185%. A rise in the free intracellular pool of dATP is thought to inhibit both rubonucleotide reduction and polynucleotide ligase, an enzyme concerned in DNA synthesis and repair. The hypothesis is suggested here that folate deficiency per se, as well as a functional folate deficiency induced by methotrexate may cause reduced DNA synthesis, megaloblastic changes, and chromosome abnormalities by producing a rise in the free intracellular pool of dATP as well as by causing a fall in free intracellular dTTP.Keywords
This publication has 14 references indexed in Scilit:
- KINETICS AND MORPHOLOGY OF HAEMOPOIESIS IN PERNICIOUS ANAEMIABritish Journal of Haematology, 1972
- Effect of Thymine Concentration on the Replication Velocity of DNA in a Thymineless Mutant of Escherichia coliNature, 1970
- A method for the determination of dATP and dTTP in picomole amountsAnalytical Biochemistry, 1970
- Single-strand breaks in bacterial DNA associated with thymine starvationJournal of Molecular Biology, 1969
- A rapid quantitative determination of deoxyribonucleoside triphosphates based on the enzymatic synthesis of DNABiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1969
- Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency in GoutAnnals of Internal Medicine, 1969
- Enzymatic breakage and joining of deoxyribonucleic acid. VI. Further purification and properties of polynucleotide ligase from Escherichia coli infected with bacteriophage T4.1968
- Deranged DNA Synthesis by Bone Marrow from Vitamin B12‐Deficient Humans*British Journal of Haematology, 1968
- Studies on the acid-soluble nucleotide pool in thymine-requiring mutants of Escherichia coli during thymine starvationBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1966
- Studies on the acid-soluble nucleotide pool in thymine-requiring mutants of Escherichia coli during thymine starvationBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1965