Assessment of individual sensitivity to ionizing radiation and DNA repair efficiency in a healthy population

Francesca Marcon, Cristina Andreoli, Sabrina Rossi, Alessandra Verdina, Rossella Galati, Riccardo Crebelli

Research output: Contribution to journalArticle

Abstract

Inter-individual variation in response to exposure to carcinogens has been ascribed to differences in carcinogen metabolism as well as to variability in DNA repair capacity (DRC). In order to investigate the role of inherited and acquired factors on individual variation in DNA repair capacity, a mutagen sensitivity assay was carried out on 31 healthy subjects. Fresh blood samples were irradiated with γ-rays (2Gy) and the kinetics of DNA repair in leukocytes assessed by the comet assay 0, 15, and 30min after irradiation. Whole blood cultures were set up to detect spontaneous and induced structural chromosomal aberrations in lymphocytes 48h after irradiation. The results obtained were evaluated with respect to age, gender, smoking habits, occupational exposure to chemicals and metabolic genotype (NQO1, GSTM1 and GSTT1) of the study subjects. A higher frequency of radiation-induced aberrations was observed in GSTM1-positive individuals compared with GSTM1-null subjects (P=0.025), as well as in non-smokers compared with heavy smokers (P=0.05). Similar results were obtained by measuring residual DNA damage (RD) shortly after irradiation by means of the comet assay, with non-smokers showing a higher amount of RD compared with smokers (P=0.016). Moreover, a significant correlation (P=0.008) was observed between the amount of RD and the frequency of chromosome breaks after irradiation. The results of this pilot study suggest a modulator effect of smoking habits and GSTM1 genotype on the individual DNA repair capacity, possibly related to the higher expression of enzymes involved in the repair of oxidative DNA damage in heavy smokers and GSTM1-null subjects.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume541
Issue number1-2
DOIs
Publication statusPublished - Nov 10 2003

Keywords

  • Challenge assay
  • Comet assay
  • DNA repair capacity
  • DRC
  • DT-diaphorase
  • Glutathione-S-transferase
  • GST
  • Ionizing radiation
  • Mutagen sensitivity
  • NQO1
  • PCR
  • Polymerase chain reaction
  • Restriction fragment length polymorphism
  • RFLP

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics
  • Molecular Biology

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