Asbestos-induced pulmonary toxicity

Role of DNA damage and apoptosis

Daya Upadhyay, David William Kamp*

*Corresponding author for this work

Research output: Contribution to journalShort survey

71 Citations (Scopus)

Abstract

Asbestos causes asbestosis and various malignancies by mechanisms that are not clearly defined. Here, we review the accumulating evidence showing that asbestos is directly genotoxic by inducing DNA strand breaks (DNA-SB) and apoptosis in relevant lung target cells. Although the exact mechanisms by which asbestos causes DNA damage and apoptosis are not firmly established, some of the implicated mechanisms include the generation of iron-derived reactive oxygen species (ROS) as well as reactive nitrogen species (RNS), alteration in the mitochondrial function, and activation of the death receptor pathway. We focus on the accumulating evidence implicating ROS. DNA repair mechanisms have a key role in limiting the extent of DNA damage. Recent studies show that asbestos activates DNA repair enzymes such as apurinic/apyrimidinic endonuclease (APE) and poly (ADP-ribose) polymerase (PARP). Asbestos-induced neoplastic transformation may result in the setting where DNA damage overwhelms DNA repair in the face of a persistent proliferative signal. Strategies aimed at limiting asbestos-induced oxidative stress may reduce DNA damage and, as such, prevent malignant transformation.

Original languageEnglish (US)
Pages (from-to)650-659
Number of pages10
JournalExperimental Biology and Medicine
Volume228
Issue number6
DOIs
StatePublished - Jan 1 2003

Fingerprint

Asbestos
DNA Damage
Toxicity
Apoptosis
Lung
DNA
DNA Repair
Reactive Oxygen Species
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA Repair Enzymes
Repair
Asbestosis
Reactive Nitrogen Species
Death Domain Receptors
DNA Breaks
Poly(ADP-ribose) Polymerases
Oxidative stress
Endonucleases
Oxidative Stress
Iron

Keywords

  • Antioxidants
  • Apoptosis
  • Apurinic/apyrimidinic endonuclease
  • Asbestos DNA damage
  • DNA strand break
  • Free radicals
  • Mitochondria
  • Poly(ADP-ribose) polymerase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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Asbestos-induced pulmonary toxicity : Role of DNA damage and apoptosis. / Upadhyay, Daya; Kamp, David William.

In: Experimental Biology and Medicine, Vol. 228, No. 6, 01.01.2003, p. 650-659.

Research output: Contribution to journalShort survey

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