title: Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women.
abstract: OBJECTIVE
  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- 1BW; 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.
authors.affiliation: Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fantini
authors.affiliation: Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", 00135, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Sgrò
authors.affiliation: Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pittaluga
authors.affiliation: Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: de Perini
authors.affiliation: Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Dimauro
authors.affiliation: Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, 20145, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sartorio
authors.affiliation: Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy. daniela.caporossi@uniroma4.it.
authors.forename: D
authors.initials: D
authors.lastname: Caporossi
authors.affiliation: Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", 00135, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Di Luigi
mesh_terms: D000328:Adult; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D064368:Healthy Volunteers; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage*; D016387:Women's Health; D055815:Young Adult
chemical_list: C583557:IGF1 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: Chromosomal aberrations; Comet assay; IGF-1; IGFBP-3