INDUCTION OF APOPTOSIS BY POLYUNSATURATED FATTY-ACIDS AND ITS RELATIONSHIP TO FATTY-ACID INHIBITION OF CARNITINE PALMITOYLTRANSFERASE-I ACTIVITY IN HEP2 CELLS

The effects of fatty acids on the induction of apoptosis were studied over a 24 hour period in Hep2 human larynx tumour cells. While oleic a nd linoleic acids had little effect on the apoptotic index, the polyun saturated fatty acids alpha-linolenic, gamma-linolenic, arachidonic, e icosapentaenoic and docosahexaenoic acids all induced apoptosis, begin ning at similar to 6 hours after fatty acid exposure. By 24 hours afte r exposure, the apoptotic index had reached as much as 19% in the pres ence of docosahexaenoic or alpha-linolenic acid. The correlation betwe en degree of unsaturation of the 18-carbon fatty acids and the apoptot ic index was r(2)=0.45, 0.89, 0.84 and 0.98 at 6, 8, 12 and 24 hours, respectively. The correlation between mitochondrial carnitine palmitoy ltransferase I (CPT I) activity, 6 hours after exposure, and the apopt otic index was r(2)=0.842 and 0.798 at 12 and 24 hours, respectively. The inhibition of CPT I and subsequent fatty acid oxidation by polyuns aturated fatty acids leads to a significant increase in apoptosis, sug gesting that CPT I may be involved in the processes of programmed cell death in Hep2 human tumour cells.