Related Experiment Video

Updated: Aug 9, 2026

Modeling Chemotherapy Resistant Leukemia In Vitro
08:41

Modeling Chemotherapy Resistant Leukemia In Vitro

Published on: February 9, 2016

Cross-sensitivity of methylating agents, hydroxyurea, and methotrexate in human tumor cells of the Mer- phenotype

K Maynard, P G Parsons

    Cancer Research
    |October 1, 1986
    PubMed

    Insights

    Sensitive tumor cells (Mer-) to methylating agents also responded to hydroxyurea (HU) and methotrexate. This drug sensitivity was retained even after developing resistance to methylating agents, suggesting therapeutic potential.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Drug Resistance

    Background:

    • The Mer- phenotype confers sensitivity to methylating agents like 5-(3-methyl-1-triazeno)imidazole-4-carboxamide.
    • Tumor cell lines exhibit varying sensitivities to chemotherapeutic agents, impacting treatment efficacy.

    Purpose of the Study:

    • To investigate the relationship between methylating agent resistance (Mer+) and sensitivity to hydroxyurea (HU) and methotrexate.
    • To explore the therapeutic implications of retained drug sensitivity in resistant cancer cells.

    Main Methods:

    • Assessed sensitivity of human tumor cell lines with Mer- and Mer+ phenotypes to HU and methotrexate.
    • Derived Mer+ cell lines in vitro and evaluated their cross-resistance patterns.
    • Investigated the effect of HU on adenovirus replication and reactivation in Mer- and Mer+ cells.

    Main Results:

    • Mer- cell lines sensitive to methylating agents were also sensitive to HU and methotrexate.
    • Mer+ cell lines, resistant to methylating agents, did not develop cross-resistance to HU or methotrexate.
    • Cell sensitivity to HU correlated with inhibition of DNA synthesis, not enhanced viral reactivation.

    Conclusions:

    • Cellular sensitivity to deoxynucleotide depletion (via HU) is linked to the Mer- phenotype.
    • The retention of HU and methotrexate sensitivity in cells developing resistance to methylating agents has potential therapeutic applications in cancer treatment.

    More Related Videos

    Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase10:33

    Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

    Published on: October 15, 2018

    Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors06:07

    Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

    Published on: August 5, 2022

    Related Concept Videos

    Mismatch Repair01:36

    Mismatch Repair

    Overview
    Targeted Cancer Therapies02:57

    Targeted Cancer Therapies

    The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
    There are several types of targeted therapies against specific...
    Treatment Resistant Cancers02:56

    Treatment Resistant Cancers

    Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
    Mismatch Repair01:20

    Mismatch Repair

    Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
    The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
    The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
    Phase II Reactions: Methylation Reactions01:17

    Phase II Reactions: Methylation Reactions

    Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
    The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
    Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

    Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

    Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...