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.

Abstract

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.

• Authors: S Cianfarani, B Tedeschi, D Germani, S P Prete, P Rossi, P Vernole, D Caporossi, B Boscherini
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 28 Issue 1 Pg. 41-7 (Jan 1998) ISSN: 0014-2972 [Print] England
• PMID: 9502186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, metabolism)
• Tumor Suppressor Protein p53 (biosynthesis)