Logo image
Back
A new assay for intracellular measurement of inosine monophosphate dehydrogenase activity: a guide for better selection of patients for enzyme-targeted chemotherapy
Journal article   Open access   Peer reviewed

A new assay for intracellular measurement of inosine monophosphate dehydrogenase activity: a guide for better selection of patients for enzyme-targeted chemotherapy

N Markovic, O Markovic, J Roberts and S Markovic
The journal of histochemistry and cytochemistry, v 42(1)
Jan 1994
DOI: https://doi.org/10.1177/42.1.7903327
PMID: 7903327
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1177/42.1.7903327View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Acute Disease Antineoplastic Agents - therapeutic use Dose-Response Relationship, Drug Drug Therapy, Computer-Assisted Humans Image Processing, Computer-Assisted IMP Dehydrogenase - metabolism Leukemia, Experimental - drug therapy Leukemia, Experimental - enzymology Leukemia, Experimental - pathology Leukemia, Myeloid - drug therapy Leukemia, Myeloid - enzymology Leukemia, Myeloid - pathology Reference Values Ribavirin - analogs & derivatives Ribavirin - therapeutic use Tumor Cells, Cultured
We developed a new cytochemical assay for identification of cells containing inosine monophosphate dehydrogenase (IMPDH) and measurement of tumor cell sensitivity to the escalating dose/schedule of the IMPDH pattern-targeting drugs. The assay is based on cytochemical principles for development of DH activity markers inside morphologically classified cells, image analysis for measuring the amount of this marker, and computer assistance for data management. The assay was optimized on a human leukemia cell line (K562-NS) and reference values for enzyme activity were established. Assay specificity was determined with different substrates and enzyme inhibitors. Sensitivity depends on the measuring instrument (image analyzing system), and the precision of the biological model used for assessment of reference values was high. IMPDH-positive malignant cells were found in all specimens obtained from acute leukemia and solid tumor patients (13/13 and 29/29) and in four human tumor cell lines (K562, K562-NS, HL60, and HL60-M). Cells of the K562-NS line were exposed to tiazofurin and ribavirin in conventional assays for assessment of drug-induced acute and subacute toxicity/sensitivity. A reduction of IMPDH activity was recorded at drug concentrations below the range at which cell damage appeared.

Metrics

6 Record Views
4 citations in Web of Science
3 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Logo image