Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women

C. Fantini, P. Sgrò, M. Pittaluga, A. de Perini, I. Dimauro, A. Sartorio, D. Caporossi, L. Di Luigi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL). Methods: Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mg kg− 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations. Results: rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST: p = 0.02; PRE vs. POST30: p = 0.007). Conclusions: This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.

Original languageEnglish
Pages (from-to)645-652
Number of pages8
JournalJournal of Endocrinological Investigation
Volume40
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Keywords

  • Chromosomal aberrations
  • Comet assay
  • IGF-1
  • IGFBP-3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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