Docosahexaenoic acid ethyl ester and its ultraviolet degradation products showed DNA-breaking activity in vitro and cytotoxic effects on the HSC-4 cell line.

The DNA-breaking activity and cytotoxicity of docosahexaenoic acid ethyl ester (DHAE) and its degradation products (dDHAE) induced by ultraviolet (UV) irradiation, were demonstrated in this study. The major component of dDHAE was identified as 4-hydroxyvaleric acid ethyl ester. DHAE and dHAE solutions at a concentration of 100 mg/ml induced single-strand breaks of plasmid DNA after an incubation at 37 degrees C and pH 7.6 for 15 hours. DHAE transformed a plasmid supercoiled DNA (Form I) into an open circular relaxed form (Form II), and dDHAE completely destroyed DNA molecules. HSC-4 cells, which were derived from human prickle cell carcinoma, were cultured with various concentrations (10, 30 and 50 micrograms/ml) of DHAE and dDHAE. Both inhibited the proliferation of HSC-4 cells. The potency of their cytotoxicity was dependent on their concentration. It is noteworthy that the lethal effects of DHAE and dDHAE on HSC-4 cells were quite similar, although the DNA-breaking activity of dDHAE was much greater than that of DHAE. These results suggested that DHAE becomes more cytotoxic after undergoing oxidization and metabolism in the cell.