Formation of DNA adducts in the aorta of smoke-exposed rats, and modulation by chemopreventive agents

Alberto Izzotti, Anna Camoirano, Cristina Cartiglia, Elena Tampa, Silvio De Flora

Research output: Contribution to journalArticlepeer-review

Abstract

Our previous studies showed that nucleotide alterations, evaluated by 32P postlabeling, are systematically detected in smooth muscle cells of atherosclerotic lesions localized in the aorta of surgical patients. The level of these molecular lesions was correlated with the occurrence of known atherogenic risk factors, among which the number of currently smoked cigarettes, and was significantly enhanced in individuals having a null GSTM1 genotype as compared to individuals carrying the GSTM1 genotype. The present study had the dual objective of evaluating the formation of DNA adducts in the whole thoracic aorta of Sprague-Dawley rats, exposed whole-body to cigarette smoke for 28 consecutive days, and of investigating the effects of chemopreventive agents given orally during the same period. High levels of 32P postlabeled DNA adducts were formed in the aorta of smoke-exposed rats, with an overall 11 times increase over the total levels observed in sham-exposed rats, and with increases ranging between three and 63 times for seven individual DNA adducts. Supplement of the diet with either 1,2-dithiole-3-thione, phenethyl isothiocyanate or 5,6-benzoflavone had no or poor effects on the smoke-related formation of nucleotide alterations in the aorta. In contrast, oltipraz, given with the diet, N-acetyl-L-cysteine, given with drinking water and, even more potently, their combination exerted remarkable protective effects. The results of this experimental study, together with the previous findings in humans, suggest that DNA alterations may contribute to the atherogenic process, clarify a possible mechanism of cigarette smoke, a well known atherogen, and show the potential protective effects of certain drugs towards these alterations.

Original languageEnglish
Pages (from-to)97-106
Number of pages10
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume494
Issue number1-2
DOIs
Publication statusPublished - Jul 25 2001

Keywords

  • Aorta
  • Atherosclerosis
  • Chemoprevention
  • Cigarette smoke
  • DNA adducts

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Formation of DNA adducts in the aorta of smoke-exposed rats, and modulation by chemopreventive agents'. Together they form a unique fingerprint.

Cite this