MELANOMA CELL DESTRUCTION IN THE MICROVASCULATURE OF PERFUSED HEARTS IS REDUCED BY PRETREATMENT WITH VITAMIN-E

Different mechanisms have been proposed to explain the rapid eliminati on of circulating malignant cells: interactions with circulating leuko cytes, mechanical trauma induced by deformation, shear forces and tiss ue pressure variations, Based on earlier observations in an isolated h eart perfusion model the present study was performed to test whether o r not microvascular damage of malignant cells depends on their anti-ox idant status. Murine melanoma B16F10 cells, pretreated with 100 mu M a lpha-tocopherol (or solvent) for 48 h, were used. The cells were perfu sed into the coronary vasculature of isolated hearts from C57/BL6 mice . Passing cells were collected and their viability determined by Trypa n Blue exclusion. The hearts were processed for electron microscopy an d the frequency of ultrastructurally intact and damaged B16 cells trap ped in capillaries was recorded. In filter perfusion experiments the e ffect of vitamin E pretreatment on the resistance of the melanoma cell s to mechanical deformation was determined. Morphometrically, cell siz e and cell profile perimeter excess of the melanoma cells were compute d. Vitamin E pretreatment increased perfused cell viability from 50% t o 81%. Ultrastructurally 30% of the intracapillary vitamin E treated c ells were damaged (plasmalemmal fragmentation or worse) as compared to 58% of control cells. These differences were statistically significan t (P<0.01) whereas no differences could be demonstrated in filterabili ty, cell size, or cell surface excess. The data support the hypothesis that malignant cell destruction in the systemic microcirculation is a t least partly dependent on an oxygen metabolite mediated process, the exact nature (e.g. superoxide, hydrogen peroxide, nitric oxide) of wh ich remains to be determined.