Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Decrease in deoxyribonucleotide triphosphate pools and induction of alkaline-labile sites in mouse bone marrow cells

Y Kasahara1, Y Nakai, D Miura

  • 1Safety Research Department, Teijin Ltd., Tokyo, Japan.

Mutation Research
|October 1, 1993
PubMed
Summary

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

High-Statistics Measurement of Collins and Sivers Asymmetries for Transversely Polarized Deuterons.

Physical review letters·2024
Same author

Final COMPASS Results on the Transverse-Spin-Dependent Azimuthal Asymmetries in the Pion-Induced Drell-Yan Process.

Physical review letters·2024
Same author

Association between low MCV in early pregnancy and perinatal mental health in the Japan Environment and Children's Study and the possible effect of iron deficiency.

Journal of affective disorders·2024
Same author

Acute fulminant myocarditis in a patient with primary Sjögren's syndrome.

Scandinavian journal of rheumatology·2018
Same author

Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·2017
Same author

Predictive models for conversion of prediabetes to diabetes.

Journal of diabetes and its complications·2017

Multiple doses of methotrexate (MTX) increase micronuclei formation by depleting deoxyribonucleotide (dNTP) pools in mouse bone marrow cells. This depletion leads to DNA damage, explaining MTX

Area of Science:

  • Toxicology
  • Genetics
  • Molecular Biology

Background:

  • Methotrexate (MTX) is a dihydrofolate reductase (DHFR) inhibitor.
  • MTX induces micronuclei, with effects amplified by multiple doses.
  • DHFR inhibition can disrupt deoxyribonucleotide (dNTP) pools.

Purpose of the Study:

  • To investigate the effect of multiple MTX doses on dNTP pool levels in mouse bone marrow.
  • To correlate dNTP pool changes with MTX-induced micronucleus formation.

Main Methods:

  • Quantification of dNTPs (dTTP, dATP, dGTP, dCTP) using High-Performance Liquid Chromatography (HPLC).
  • Assessment of DNA strand breaks and alkaline-labile sites using alkaline elution assays.
  • Administration of MTX at 4 mg/kg/day and 100 mg/kg to mice.

Related Experiment Videos

Main Results:

  • Multiple MTX doses significantly decreased dTTP, dATP, and dGTP levels in mouse bone marrow cells.
  • A high dose of MTX (100 mg/kg) nearly eliminated dTTP levels.
  • MTX treatment generated alkaline-labile sites in mouse bone marrow DNA.

Conclusions:

  • The decrease in dNTP pools is a key mechanism underlying MTX's multiple-dose genotoxicity.
  • MTX-induced dNTP depletion leads to DNA damage, likely through apurinic/apyrimidinic sites.
  • These findings elucidate the molecular basis of MTX genotoxicity and micronucleus induction.