Melanoma cell destruction in the microvasculature of perfused hearts is reduced by pretreatment with vitamin E.

Abstract

Different mechanisms have been proposed to explain the rapid elimination of circulating malignant cells: interactions with circulating leukocytes, mechanical trauma induced by deformation, shear forces and tissue pressure variations. Based on earlier observations in an isolated heart perfusion model the present study was performed to test whether or not microvascular damage of malignant cells depends on their anti-oxidant status. Murine melanoma B16F10 cells, pretreated with 100 microM alpha-tocopherol (or solvent) for 48 h, were used. The cells were perfused into the coronary vasculature of isolated hearts from C57/BL6 mice. Passing cells were collected and their viability determined by Trypan Blue exclusion. The hearts were processed for electron microscopy and the frequency of ultrastructurally intact and damaged B16 cells trapped in capillaries was recorded. In filter perfusion experiments the effect of vitamin E pretreatment on the resistance of the melanoma cells to mechanical deformation was determined. Morphometrically, cell size and cell profile perimeter excess of the melanoma cells were computed. Vitamin E pretreatment increased perfused cell viability from 50% to 81%. Ultrastructurally 30% of the intracapillary vitamin E treated cells were damaged (plasmalemmal fragmentation or worse) as compared to 58% of control cells. These differences were statistically significant (P < 0.01) whereas no differences could be demonstrated in filterability, cell size, or cell surface excess. The data support the hypothesis that malignant cell destruction in the systemic microcirculation is at least partly dependent on an oxygen metabolite mediated process, the exact nature (e.g. superoxide, hydrogen peroxide, nitric oxide) of which remains to be determined.