Adaptive response in human cells

Induction of AP-Endonuclease by sublethal levels of reactive oxygen-species

C. V. Ramana, Istvan Boldogh, T. Izumi, R. Roy, S. Mitra

Research output: Contribution to journalArticle

Abstract

AP-endonuclease (APE) plays a key role in base excision repair (BER) by removing both abasic sites and damaged 3' termini from single-strand breaks in DNA generated by reactive oxygen species (ROS) and ionizing radiation (IR). APE-1 {APEX, HAP1) is the predominant human AP-repair enzyme. The human APE-1 gene is induced in two human cell lines by sublethal levels of ROS, e.g., HOC1 and #2O2, (but not by alkylating agents or UV light), resulting in a 5- to 12-fold increase in mRNA and protein levels at 9 to 12 h after exposure to ROS. The treated cells are more resistant (3- to 5-fold increase in D0 to MMS and bleomycin, and slightly more resistant to 7-rays than the untreated control. Resistance to UV light and HOC1 is not affected by the treatment. These results indicate that human cells may respond to sublethal ROS exposure by activating APE and BER, thereby developing resistance to toxic levels of oxidative stress. This "adaptive response" does not apply to UV light treatment, where induced DNA damage is not repaired by the BER pathway. The possibility that the cytocidal effect of HOC1 is not due to DNA damage may explain the lack of HOC1 resistance in adapted cells. This first report of adaptive response in mammalian cells is distinct from their nonspecific response to toxic doses of DNA-damaging agents.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

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DNA-(Apurinic or Apyrimidinic Site) Lyase
reactive oxygen species
Reactive Oxygen Species
Repair
Ultraviolet Rays
DNA repair
Cells
DNA Repair
Ultraviolet radiation
ultraviolet radiation
Poisons
DNA
DNA damage
DNA Damage
cells
Single-Stranded DNA Breaks
Oxidative stress
human cell lines
Alkylating Agents
Ionizing radiation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Adaptive response in human cells : Induction of AP-Endonuclease by sublethal levels of reactive oxygen-species. / Ramana, C. V.; Boldogh, Istvan; Izumi, T.; Roy, R.; Mitra, S.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

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