In vitro effects of growth hormone (GH) and insulin-like growth factor I and II (IGF-I and -II) on chromosome fragility and p53 protein expression in human lymphocytes

Eur J Clin Invest. 1998 Jan;28(1):41-7. doi: 10.1046/j.1365-2362.1998.00247.x.


Background: We have reported previously that growth hormone (GH) therapy increases cell radiosensitivity; in this study we tested whether GH itself or IGFs induce chromosome aberrations and investigated the expression of p53 protein in response to DNA damage.

Methods: Human peripheral blood lymphocytes were incubated with GH [100 and 1000 microg L(-1)], insulin-like growth factor I [IGF-I; 150 and 1000 microg L(-1)] and IGF-II [600 and 1200 microg L(-1)] for 24 h. The radiomimetic agent bleomycin [BLM; 5 microgm L(-1)] was added in the last 3 h. Cytogenetic analysis was performed by assessing the percentages of damaged cells (%DC) and chromosome aberrations (%CA). The expression of p53 was investigated by flow cytometric assay using the monoclonal antibody DO-7, and expressed as percentage positive cells and mean fluorescence intensity.

Results: BLM significantly increased both percentage DC and percentage CA and p53 expression (P < 0.01). The %DC was unaffected by the tested peptides. IGF-I [150 microg L(-1)] increased spontaneous percentage CA (P < 0.01). All peptides further increased the BLM-induced chromosome breakage: GH 100 and 1000 microg L(-1) by 30% and 73% respectively, IGF-I 150 and 1000 microg L(-1) by 41% and 96% respectively and IGF-II 600 and 1200 microg L(-1) by 89% and 45% respectively. The spontaneous and BLM-induced expression of p53 was unaffected by GH, whereas it was significantly increased by IGFs (P < 0001).

Conclusions: These results indicate that the DNA-damaging effect of BLM is amplified by GH and, more markedly, IGF-I and -II. IGF-I and -II also stimulate p53 protein expression that, taking part in DNA repair, may counteract the IGF action on genome stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bleomycin / pharmacology
  • Cells, Cultured
  • Chromosome Fragility*
  • Cytogenetics
  • Human Growth Hormone / pharmacology*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor II / pharmacology*
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism*
  • Tumor Suppressor Protein p53 / biosynthesis*


  • Tumor Suppressor Protein p53
  • Bleomycin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II