IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Liver oncogenic potential of prolonged growth hormone (GH)-administration to growing mice
Autor/es:
VERONICA GABRIELA PIAZZA; MARIANA ANDREA BOJORGE; JOHANNA GABRIELA MIQUET; ANA ISABEL SOTELO; NADIA SOFIA CICCONI; LORENA GONZALEZ
Lugar:
Mar del Plata
Reunión:
Congreso; LXIII REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA (SAIC); 2018
Resumen:
Growth hormone (GH) participates in multiple biological processes, including growth and metabolism; it is thus administered to children with growth deficiency and to adults under catabolic states, even if they are not GH-deficient. Due to its mitogenic and antiapoptotic activities, there is growing concern on its pro-tumorigenic potential as an adverse effect of its administration in the long term. To evaluate GH treatment on liver tumor formation, male mice were treated with GH during the growth period. Since GH is not a potent mitogen per se, a hepatic tumor inductor, diethylnitrosamine (DEN), was also administered before weaning.Livers were removed at 48 weeks of age and were inspected for nodular lesions that differ from the surrounding liver parenchyma regarding size, color and texture. Only groups receiving DEN developed macroscopic tumors; GH-treatment alone did not induce tumor-formation, but given with DEN, increased the number of hepatic lesions. Liver sections were analyzed in search of preneoplastic morphological alterations. DEN-treated groups exhibited microscopically dysplastic foci whereas GH-treatment alone did not generate such alterations. The number of hepatocytes per microscopic field was increased in the dysplastic foci compared to the surrounding tissue, denoting smaller cell size inside the foci. Mice treated with GH exhibited larger cell size inside the dysplastic foci, compared to the non-GH-treated DEN-group. To evaluate hepatocellular proliferation, the expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. GH-treated groups exhibited a small although non-significant increase of PCNA positive nuclei. Increased cell proliferation was also observed inside dysplastic foci, although differences were significant only in animals that did not receive GH treatment.Consequently, GH-treatment to growing mice per se does not promote tumor formation when the hormone is administered during the growth period at a therapeutic dose. However, GH-treatment could facilitate a pro-tumorigenic environment that would promote carcinogenesis.