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

S. Cianfarani, B. Tedeschi, D. Germani, S. P. Prete, P. Rossi, P. Vernole, D. Caporossi, B. Boscherini

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 μg L -1), insulin-like growth factor I (IGF-I; 150 and 1000 μg L -1) and IGF-II (600 and 1200 μg L -1) for 24 h. The radiomimetic agent bleomycin (BLM; 5 μg mL -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 μg L -1) increased spontaneous percentage CA (P <0.01). All peptides further increased the BLM-induced chromosome breakage: GH 100 and 1000 μg L -1 by 30% and 73% respectively, IGF-I 150 and 1000 μg L -1 by 41% and 96% respectively and IGF-II 600 and 1200 μg 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 <0.001). 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.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalEuropean Journal of Clinical Investigation
Volume28
Issue number1
DOIs
Publication statusPublished - 1998

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Chromosome Fragility
Insulin-Like Growth Factor II
Lymphocytes
Chromosomes
Insulin-Like Growth Factor I
Growth Hormone
Proteins
Aberrations
Chromosome Aberrations
DNA
Chromosome Breakage
Peptides
Genomic Instability
Cytogenetic Analysis
Radiation Tolerance
Bleomycin
Cell- and Tissue-Based Therapy
DNA Repair
DNA Damage
In Vitro Techniques

Keywords

  • Bleomycin
  • Chromosome aberrations
  • DNA repair
  • GH
  • IGF-I
  • IGF-II
  • Radiosensitivity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Cianfarani, S.; Tedeschi, B.; Germani, D.; Prete, S. P.; Rossi, P.; Vernole, P.; Caporossi, D.; Boscherini, B.

In: European Journal of Clinical Investigation, Vol. 28, No. 1, 1998, p. 41-47.

Research output: Contribution to journalArticle

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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 μg L -1), insulin-like growth factor I (IGF-I; 150 and 1000 μg L -1) and IGF-II (600 and 1200 μg L -1) for 24 h. The radiomimetic agent bleomycin (BLM; 5 μg mL -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 μg L -1) increased spontaneous percentage CA (P <0.01). All peptides further increased the BLM-induced chromosome breakage: GH 100 and 1000 μg L -1 by 30{\%} and 73{\%} respectively, IGF-I 150 and 1000 μg L -1 by 41{\%} and 96{\%} respectively and IGF-II 600 and 1200 μg 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 <0.001). 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.",
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author = "S. Cianfarani and B. Tedeschi and D. Germani and Prete, {S. P.} and P. Rossi and P. Vernole and D. Caporossi and B. Boscherini",
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T1 - 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

AU - Cianfarani, S.

AU - Tedeschi, B.

AU - Germani, D.

AU - Prete, S. P.

AU - Rossi, P.

AU - Vernole, P.

AU - Caporossi, D.

AU - Boscherini, B.

PY - 1998

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N2 - 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 μg L -1), insulin-like growth factor I (IGF-I; 150 and 1000 μg L -1) and IGF-II (600 and 1200 μg L -1) for 24 h. The radiomimetic agent bleomycin (BLM; 5 μg mL -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 μg L -1) increased spontaneous percentage CA (P <0.01). All peptides further increased the BLM-induced chromosome breakage: GH 100 and 1000 μg L -1 by 30% and 73% respectively, IGF-I 150 and 1000 μg L -1 by 41% and 96% respectively and IGF-II 600 and 1200 μg 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 <0.001). 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.

AB - 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 μg L -1), insulin-like growth factor I (IGF-I; 150 and 1000 μg L -1) and IGF-II (600 and 1200 μg L -1) for 24 h. The radiomimetic agent bleomycin (BLM; 5 μg mL -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 μg L -1) increased spontaneous percentage CA (P <0.01). All peptides further increased the BLM-induced chromosome breakage: GH 100 and 1000 μg L -1 by 30% and 73% respectively, IGF-I 150 and 1000 μg L -1 by 41% and 96% respectively and IGF-II 600 and 1200 μg 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 <0.001). 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.

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KW - Radiosensitivity

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