Human Growth Hormone (hGH) May Influence Chromosome Aberrations and Fragility 487

Abstract

The influence of hGH treatment on spontaneous chromosome aberrations and chromosome fragility was tested in 23 naive patients aged 4 to 16 years. The breaking action of ionizing radiation was used as an indicator of chromosome fragility. 17 patients had growth hormone deficiency, 1 Turner syndrome, and 5 neurosecretory growth hormone dysfunction. Blood samples were taken at baseline and following 6 months of hGH treatment (0.3 mg/Kg/week). Lymphocyte cultures and cytogenetic preparations were established using standard cytogenetic techniques. Half of the cultures were irradiated with 3 Gy of gamma rays. All mitotic preparations were coded to ensure “blind” enumeration of aberrations. A one-way ANOVA was performed on log transformed data for analysis of aberrations per cell. There were no significant differences between pre-treatment (9,500 cells) and post-treatment (8,000 cells) cells for spontaneous chromosome-type aberrations (mean ± SEM) 4.2 × 10-3 ± 1.2 × 10-3 vs 7.9 × 10-3 ± 2.9 × 10-3 (p=0.08); for chromatid-type aberrations 9.2 × 10-3 ± 2.8 × 10-3 vs 1.1× 10-2 ± 4.0 × 10-3 (p=0.42); and for total aberrations (chromosome + chromatid) 1.3 × 10-2 ± 3.0× 10-3 vs 1.9 × 10-2 ± 7.0 × 10-3 (p=0.10). There were also no significant differences for radiation-induced aberrations (4,550 pretreatment cells and 4,850 post-treatment cells) for chromosome aberrations 1.12 ± 3.0 × 10-2 vs 1.05 ± 5.0 × 10-2 (p=0.18); for chromatid aberrations 2.6 × 10-2 ± 5.0 × 10-3 vs 2.0× 10-2 ± 3.0 × 10-3 (p=0.60); and for total aberrations 1.15 ± 3.0 × 10-2 vs 1.07 ± 5.0 × 10-2 (p=0.17). However, when the data were analyzed on a per chromosome basis (i.e. number of aberrant chromosomes ÷ total number of chromosomes scored) with binomial probability being applied to the raw data, small but significant differences were seen. Total spontaneous aberrations per cell (mean with 95% confidence limits) were: pre-treatment 2.65 × 10-4 (2.18 × 10-4 to 3.13 × 10-4) vs post-treatment 3.42 × 10-4 (2.83 × 10-4 to 4.02× 10-4) p<0.05), and for total radiation-induced aberrations 2.51 × 10-2 (2.44 × 10-2 to 2.57 × 10-2) vs 2.40 × 10-2 (2.34 × 10-2 to 2.47× 10-2) (p<0.05). This analysis suggests that 6 months of hGH treatment may lead to a significant increase in spontaneous chromosome aberrations and significant decrease in chromosome fragility. The disparity between the chromosome aberration and fragility data is unexplained and requires further investigation.