DNA fragmentation, DNA-protein crosslinks, 32P postlabeled nucleotidic modifications, and 8-hydroxy-2'-deoxyguanosine in the lung but not in the liver of rats receiving intratracheal instillations of chromium(VI). Chemoprevention by oral N-acetylcysteine

Alberto Izzotti, Maria Bagnasco, Anna Camoirano, Michele Orlando, Silvio De Flora

Research output: Contribution to journalArticlepeer-review

Abstract

An in vivo study was carried out with the objectives of evaluating (a) the localization of DNA lesions resulting from exposure to chromium(VI) by the respiratory route, (b) the molecular nature of DNA alterations, and (c) modulation of DNA damage by a known chemopreventive agent. To this purpose, Sprague-Dawley rats received intratracheal instillations of sodium dichromate (0.25 mg/kg body weight) for three consecutive days, and the day after the last treatment lung and liver were removed for DNA purification. The results showed a selective localization of DNA lesions in the lung but not in the liver, which can be ascribed to toxicokinetics and metabolic characteristics of chromium(VI). DNA alterations included DNA-protein crosslinks, DNA fragmentation, nucleotidic modifications, and 8-hydroxy-2'-deoxyguanosine. The last two endpoints were evaluated, for the first time in chromium toxicology, by means of 32P postlabeling procedures. This methodology was adapted to the detection of the DNA damage produced by those reactive oxygen species which result from the intracellular reduction of chromium(VI). The oral administration of the thiol N-acetylcysteine completely prevented any induction of DNA lesions in lung cells.

Original languageEnglish
Pages (from-to)233-244
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume400
Issue number1-2
DOIs
Publication statusPublished - May 25 1998

Keywords

  • 8-Hydroxy-2'-deoxyguanosine
  • P postlabeling
  • Chromium(VI)
  • DNA fragmentation
  • DNA-protein crosslink
  • N-acetylcysteine
  • Nucleotidic modification

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

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