Histamine as a radiosensitizer of malignant cell lines.

E.S. RIVERA; V. MEDINA; G. CRICCO; N. MOHAMAD; M. CROCCI; G. MARTIN; M NÚÑEZ; RM BERGOC

Madrid, Spain.

Congreso; XI International Radioprotection Congress of the International Radiation Protection Association.; 2004

nternational Radiation Protection Association.

It has been established that the treatment with Histamine (Hi) produces a significant growth inhibition of different cell lines derived from human neoplasias. In a model of Knockout mice completely depleted of endogenous Hi, it was observed a significant delay in bone marrow repopulation after whole body irradiation. These results are in agreement with the hypothesis that histamine has a role in the regulation of haematopoiesis as well as an inhibitory effect on apoptosis. The objective of this paper was to study the possible effect of Hi as protector of normal cells and radiosensitizer of malignant ones. To study the effect of Hi on small-intestine and bone marrow, thirty nude mice were randomly separated into two groups: Control irradiated (C), and irradiated receiving Histamine (Hi-group). All animals received a single dose of 10 Gy on whole-body employing a 137 Cs source of 189 TBq (Dose rate: 7.7 Gy/min) calibrated with TLD 700 dosimeter. Hi-group received a daily sc injection (0.1 mg/kg) starting 20 hs before irr adiation. Mice were sacrificed 5 days after irradiation. Histopathological analysis indicated that intestinal mucosae of C group showed important injury, whilst mucosae of Hi-treated mice showed mild mucosal atrophy with conservation of villous projections and absence of vascular congestive changes. In order to investigate the effect of Hi on radiosensitivity of transformed cells, MDA-MB-231 (human breast carcinoma cells) were irradiated in vitro with doses ranging from 0 to 10 Gy. Results of radiobiological parameters indicate a significant increase on radiosentivity of malignant cells. Employing specific fluorescent dyes and flow cytometric analysis we determined that the intracellular levels of hydrogen peroxide (H2O2) are significantly increased by Hi 10 µM in control and also in irradiated MDA-MB-231 cells, while the levels of superoxide (SO2) were not significantly modified by Hi-treatment.poster