C Fantini1, P Sgrò2, M Pittaluga1, A de Perini1, I Dimauro1, A Sartorio3, D Caporossi4, L Di Luigi2. 1. Unit of Biology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy. 2. Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università di Roma "Foro Italico", 00135, Rome, Italy. 3. Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, 20145, Milan, Italy. 4. 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.
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.
RCT Entities:
PURPOSE: While a good safety for recombinant humangrowth 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.
Authors: L Di Luigi; C Baldari; F Pigozzi; G P Emerenziani; M C Gallotta; F Iellamo; E Ciminelli; P Sgrò; F Romanelli; A Lenzi; L Guidetti Journal: Int J Sports Med Date: 2007-07-05 Impact factor: 3.118
Authors: Natasha M Appelman-Dijkstra; Kim M J A Claessen; Ferdinand Roelfsema; Alberto M Pereira; Nienke R Biermasz Journal: Eur J Endocrinol Date: 2013-05-28 Impact factor: 6.664
Authors: Maria Reyes Beltran Valls; Ivan Dimauro; Andrea Brunelli; Eliana Tranchita; Emanuela Ciminelli; Paolo Caserotti; Guglielmo Duranti; Stefania Sabatini; Paolo Parisi; Attilio Parisi; Daniela Caporossi Journal: Age (Dordr) Date: 2013-10-18