Tumor Biology

, Volume 33, Issue 3, pp 739–748 | Cite as

Long-term adaptation of the human lung tumor cell line A549 to increasing concentrations of hydrogen peroxide

  • Abdullah Onul
  • Kim M. Elseth
  • Humberto De Vitto
  • William A. Paradise
  • Benjamin J. Vesper
  • Gabor Tarjan
  • G. Kenneth HainesIII
  • Franklin D. Rumjanek
  • James A. Radosevich
Research Article


Previously, we demonstrated that A549, a human lung cancer cell line, could be adapted to the free radical nitric oxide (NO). NO is known to be over expressed in human tumors. The original cell line, A549 (parent), and the newly adapted A549-HNO (which has a more aggressive phenotype) serve as a useful model system to study the biology of NO. To see if tumor cells can similarly be adapted to any free radical with the same outcome, herein we successfully adapted A549 cells to high levels of hydrogen peroxide (HHP). A549-HHP, the resulting cell line, was more resistant and grew better then the parent cell line, and showed the following characteristics: (1) resistance to hydrogen peroxide, (2) resistance to NO, (3) growth with and without hydrogen peroxide, and (4) resistance to doxorubicin. Gene chip analysis was used to determine the global gene expression changes between A549-parent and A549-HHP and revealed significant changes in the expression of over 1,700 genes. This gene profile was markedly different from that obtained from the A549-HNO cell line. The mitochondrial DNA content of the A549-HHP line determined by quantitative PCR favored a change for a more anaerobic metabolic profile. Our findings suggest that any free radical can induce resistance to other free radicals; this is especially important given that radiation therapy and many chemotherapeutic agents exert their effect via free radicals. Utilizing this model system to better understand the role of free radicals in tumor biology will help to develop new therapeutic approaches to treat lung cancer.


Adenocarcinoma Lung cancer Reactive oxygen species (ROS) Hydrogen peroxide Nitric oxide Cross-resistance Cellular adaptation 



The authors wish to thank Dr. Zarema Arbieva, Ms. WeiHua Wang, and Mr. Oleksiy Karpenko at the University of Illinois at Chicago Core Genomics Facility for their assistance in conducting the gene chip experiments. The authors would also like to thank Ms. Falise Platt for her assistance in preparing this manuscript.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  • Abdullah Onul
    • 1
    • 2
  • Kim M. Elseth
    • 1
    • 2
  • Humberto De Vitto
    • 1
    • 2
    • 3
  • William A. Paradise
    • 1
    • 2
  • Benjamin J. Vesper
    • 1
    • 2
  • Gabor Tarjan
    • 5
  • G. Kenneth HainesIII
    • 6
  • Franklin D. Rumjanek
    • 3
  • James A. Radosevich
    • 1
    • 2
    • 4
  1. 1.Center for Molecular Biology of Oral Diseases, College of DentistryUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Jesse Brown VAMCChicagoUSA
  3. 3.Universidade Federal do Rio de Janeiro, IbqMRio de JaneiroBrazil
  4. 4.Oral Medicine and Diagnostic Sciences, College of DentistryUniversity of Illinois at ChicagoChicagoUSA
  5. 5.Department of Pathology, John H. Stroger, Jr.Hospital of Cook CountyChicagoUSA
  6. 6.Department of PathologyYale University School of MedicineNew HavenUSA

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