INHIBITION OF MELANOMA B16-F10 GROWTH BY LIPID-PEROXIDATION PRODUCT 4-HYDROXYNONENAL

Since a gradual benign-to-malignant progression of murine melanoma B16 after exposure in vitro to hypoxia was described recently, the aim of this study was to test if exposing melanoma B16-F10 cells to aldehyde 4-hydroxynonenal (HNE), which is considered not only as one of the ma jor ''second toxic messengers'' of oxygen free radicals (or oxidative stress), but as a normal constituent of many cells and tissues, might have opposite effects. Treatment of the tumor cells with 50 mu M HNE i n vitro or in vivo did not prevent development of the tumors, but inhi bited their growth. Tumor growth inhibition was equal for in vitro and in vivo treatment, but appeared after a delay of almost one week sinc e there was no difference of the tumor volume to the control observed during the initial period of the tumor growth. Similarly, both HNE tre atment of the tumor cells before transplantation and HNE treatment of the melanoma bearing mice resulted in equally prolonged survival time. Thus, the results obtained suggest that while hypoxia could increase the malignancy of the murine melanoma cells, exposing these cells to o ne of the major ''second toxic messengers'' of oxygen free radicals, H NE, has almost opposite effects and further indicate the possible use of the aldehyde in vivo.