INCREASED CHROMOSOME FRAGILITY IN LYMPHOCYTES OF SHORT NORMAL CHILDREN TREATED WITH RECOMBINANT HUMAN GROWTH HORMONE

Abstract

The report, few years ago, of some growth hormone-deficient children having developed leukemia following therapy with human growth hormone, raised concern about a possible stimulatory effect of this therapy on tumor development. Since it is known that proneness to cancer is related to chromosome breakage, we decided to investigate whether recombinant human growth hormone (rhGH) therapy might increase chromosome fragility. Ten short-normal children (age: 6-11 yrs. mean height: −2.5 SD; mean growth rate: 4.1 cm/yr; mean bone age: −2.5 SD) were studied. Lymphocytes were collected at 0, 6 and 12 months of therapy, and the rate of spontaneous chromosome aberrations, the frequency of sister chromatid exchanges, the proiterative rate indices, the expression of common fragile sites induced by aphidicolin, and the sensitivity towards the radiomimetic action of bleomicin (BLM) were assessed. The mean frequency of BLM-induced chromosome aberrations increased from the pretherapy 0.11 breaks/cell (b/c) value to 0.23 b/c at 6 months of therapy (p<0.01), and remained at the same level (0.22 b/c) at 12 months. The frequency of damaged cells, showed a significative difference (p<0.05) between the pretherapy value (0.09) and the value found in the cultures performed at 6 and 12 months of therapy (0.14). An increase in spontaneous chromosome rearrangements at 6 and 12 months of therapy was also observed. These findings are supported by data obtained from the analysis of 16 short normal children already on rhGH therapy. Our data point out the need for rhGH to be given only in the strictest of indications. The opportunity of starting rhGH therapy should be carefully questioned when short stature is associated with conditions at risk for the development of tumours, for an increased chromosomal radiosensitivity, e.g. Down syndrome, or tor increased chromosomal breakage, e.g. Fanconi anemia and Bloom syndrome.