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Article

Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance

  • Authors:
    • Margaret E. Tome
    • Jennifer B. Frye
    • Donna L. Coyle
    • Elaine L. Jacobson
    • Betty K. Samulitis
    • Katerina Dvorak
    • Robert T. Dorr
    • Margaret M. Briehl
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, University of Arizona, Tucson, AZ 85724, USA, Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA, Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA
  • Pages: 845-852
    |
    Published online on: February 14, 2012
       https://doi.org/10.3892/etm.2012.487
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Abstract

Chronic inflammation increases lymphoma risk. Chronic inflammation exposes cells to increased reactive oxygen species (ROS). Constant exposure to ROS selects for oxidative stress-resistant cells with upregulated anti-oxidant defense enzymes. The impact of oxidative stress resistance on the redox biology and chemotherapy response in lymphoma has not been rigorously tested. To measure the effect of anti-oxidant defense enzyme upregulation in lymphoid cells, we created oxidative stress-resistant WEHI7.2 thymic lymphoma cell variants. We selected a population of WEHI7.2 cells for resistance to hydrogen peroxide and constructed catalase-overexpressing WEHI7.2 transfectants. The WEHI7.2 variants had: i) increased catalase and total superoxide dismutase activities; ii) an altered GSSG/2GSH redox potential; iii) a more oxidized NADP+/NADPH pool; and iv) increased phase 2 enzymes, NAD(P)H:quinone oxidoreductase and glutathione S-transferases μ and π. Regression analysis showed a correlation between the GSSG/2GSH redox potential and the increased phase 2 enzyme activities. As predicted from the anti-oxidant defense enzyme profile, the variants were more resistant to the oxidants hydrogen peroxide and paraquat. The variants exhibited resistance to the common lymphoma chemotherapeutics, cyclophosphamide, doxorubicin, vincristine and glucocorticoids. These data indicate that chronic ROS exposure results in lymphoid cells with multiple changes in their redox biology and a chemoresistance phenotype. These data further suggest that lymphomas that arise at the site of chronic inflammation develop chemoresistance due to a combination of drug detoxification and removal of ROS.
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Copy and paste a formatted citation
Spandidos Publications style
Tome ME, Frye JB, Coyle DL, Jacobson EL, Samulitis BK, Dvorak K, Dorr RT and Briehl MM: Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance. Exp Ther Med 3: 845-852, 2012.
APA
Tome, M.E., Frye, J.B., Coyle, D.L., Jacobson, E.L., Samulitis, B.K., Dvorak, K. ... Briehl, M.M. (2012). Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance. Experimental and Therapeutic Medicine, 3, 845-852. https://doi.org/10.3892/etm.2012.487
MLA
Tome, M. E., Frye, J. B., Coyle, D. L., Jacobson, E. L., Samulitis, B. K., Dvorak, K., Dorr, R. T., Briehl, M. M."Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance". Experimental and Therapeutic Medicine 3.5 (2012): 845-852.
Chicago
Tome, M. E., Frye, J. B., Coyle, D. L., Jacobson, E. L., Samulitis, B. K., Dvorak, K., Dorr, R. T., Briehl, M. M."Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance". Experimental and Therapeutic Medicine 3, no. 5 (2012): 845-852. https://doi.org/10.3892/etm.2012.487
Copy and paste a formatted citation
x
Spandidos Publications style
Tome ME, Frye JB, Coyle DL, Jacobson EL, Samulitis BK, Dvorak K, Dorr RT and Briehl MM: Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance. Exp Ther Med 3: 845-852, 2012.
APA
Tome, M.E., Frye, J.B., Coyle, D.L., Jacobson, E.L., Samulitis, B.K., Dvorak, K. ... Briehl, M.M. (2012). Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance. Experimental and Therapeutic Medicine, 3, 845-852. https://doi.org/10.3892/etm.2012.487
MLA
Tome, M. E., Frye, J. B., Coyle, D. L., Jacobson, E. L., Samulitis, B. K., Dvorak, K., Dorr, R. T., Briehl, M. M."Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance". Experimental and Therapeutic Medicine 3.5 (2012): 845-852.
Chicago
Tome, M. E., Frye, J. B., Coyle, D. L., Jacobson, E. L., Samulitis, B. K., Dvorak, K., Dorr, R. T., Briehl, M. M."Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance". Experimental and Therapeutic Medicine 3, no. 5 (2012): 845-852. https://doi.org/10.3892/etm.2012.487
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