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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance.

Authors: Tome, Margaret E; Frye, Jennifer B; Coyle, Donna L; Jacobson, Elaine L; Samulitis, Betty K; Dvorak, Katerina; Dorr, Robert T; Briehl, Margaret M

Published In Exp Ther Med, (2012 May)

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 antioxidant 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.

PubMed ID: 22529877 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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