Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly

Growth Horm IGF Res. 2014 Feb;24(1):29-34. doi: 10.1016/j.ghir.2013.12.002. Epub 2013 Dec 14.

Abstract

Objective: The objectives of this study were to assess cytokinesis-block micronucleus cytome (CBMN Cyt) assay parameters and also oxidative DNA damage in patients with active acromegaly and controls and to assess the relationship between age, serum insulin-like growth factor 1 (IGF-1) levels, pituitary adenoma diameters, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and CBMN Cyt assay parameters in patients with active acromegaly.

Design: The study population included 30 patients with active acromegaly and 30 age- and sex-matched healthy controls. CBMN Cyt assay parameters in peripheral blood lymphocytes of patients with active acromegaly and controls were evaluated and plasma 8-OHdG levels were measured.

Results: Frequencies of micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p<0.001, p<0.001, p<0.001, respectively). The frequencies of apoptotic and necrotic cells in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p<0.001 and p<0.001 respectively). No statistically significant differences in the number of cells in metaphase, the number of bi-nucleated cells (M2), the number of tri-nucleated cells (M3), the number of tetra-nucleated cells (M4) and nuclear division index (NDI) values were observed between patients and controls (p>0.05). Plasma 8-OHdG (ng/ml) levels in patients with acromegaly were found to be significantly higher than those in controls (p<0.005). MN frequency in the lymphocytes of patients with acromegaly increased with elevated serum IGF-1 levels (p<0.05), whereas the number of NPBs and the frequency of apoptotic cells decreased with elevated serum IGF-1 levels (p<0.01 and p<0.05 respectively).

Conclusions: Both the increase in chromosomal/oxidative DNA damage and the positive association between MN frequency and serum IGF-1 levels may predict an increased risk of malignancy in acromegalic patients. Long-term follow-up of patients with acromegaly will be necessary to establish the degree of cancer risk in this population.

Keywords: 8-OHdG levels; Acromegaly; CBMN Cyt assay; IGF-1; MN frequency.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Acromegaly / blood*
  • Acromegaly / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers / metabolism*
  • Case-Control Studies
  • Cell Nucleus / genetics
  • Cell Nucleus / pathology
  • DNA Damage / genetics*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Female
  • Follow-Up Studies
  • Genomic Instability*
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Lymphocytes / pathology
  • Male
  • Micronucleus Tests
  • Middle Aged
  • Necrosis
  • Prognosis

Substances

  • Biomarkers
  • Insulin-Like Growth Factor I
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine