Histamine (HA) Action in Rat Mammary Gland Malignant Transformation.

MOHAMAD N; GUTIÉRREZ A; NUÑEZ M.; GENRE F; MEDINA V; RIVERA E; CRICCO G; MARTÍN G

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Annual Meeting of SAIB, Sociedad Argentina de Investigación en Bioquímica y Biología Molecular,; 2007

Histamine (HA) action in rat mammary gland malignant transformation. Mohamad M, Gutiérrez A, Núñez M, Genre F, Croci M, Medina V, Bergoc R, Rivera E, Cricco G, Martín G. We have previously shown that ranitidine (Ran, H2 antagonist), decreased while Loratadine (Lor, H1 antagonist) increased growth of NMU-induced mammary carcinomas in rats. The aim of this work was to evaluate the effect of HA, Ran and Lor in mammary gland of NMU injected rats during malignant progression. Four groups of rats were used: NMU (control); NMU/HA; NMU/Lor; NMU/Ran. NMU was injected at 55, 80 and 110 days of age and treatments began 7 days before. Histological differences were observed starting at 55 days: Control, HA and Lor groups showed important ductal proliferation with ramifications, frequent terminal end buds, anisocariosis and multi-stratified layers. Instead, Ran group showed milder ductal proliferation and anisocariosis as well as mono-layered ducts. At 110 and 160 days the difference between Ran and control was even more pronounced. Meanwhile, HA and Lor treated tissues exhibit signs of transformation: ductal dysplasia, hyperplasia and papilomatosis as well as focii of carcinoma; changes jwere observed in Controls to a lesser extent. In addition, HA and Lor treatment produced a significant increase in plasma insulin levels. Ran decreased IGF-1 and insulin receptor expression in ductal cells. Results suggest that HA may play an important role in mammary gland carcinogenesis not only by a direct action on cell growth but also modulating the IGFs system.