I-131-lipiodol cytotoxicity in hepatoma cells

Hepatoma is a common cancer in Taiwan. New effective treatment for hepatoma patients is urgently needed. Encouraging results of I-131-lipiodol treatment for hepatoma with minimal toxicity have been recently reported. The mechanism of lipiodol targeting and retention by hepatoma are not well understood. The cellular interaction of lipiodol and the cytotoxic effects of I-131-lipiodol on hepatoma cells were investigated in this study. HepG2 cells were cultured with lipiodol, and untreated HepG2 cells were used as the control. Changes of cellular morphology were accessed by light and electron microscopy. The uptake and retention of lipiodol by HepG2 cells were studied by phase contrast microscopy and neutron activation analysis. HepG2 cells were cultured with I-131-lipiodol varying from 0.12 microCi to 120 microCi. The cytotoxic effect of I-131-lipiodol was evaluated by the surviving fraction of HepG2 cells. Changes in cellular morphology was examined by light microscopy. Results indicated that HepG2 cells were capable of active uptake of large amounts of lipiodol by endocytosis and prolonged intra-cellular retention associated with the formation of many bulging cytoplasmic extensions. I-131-lipiodol was highly cytotoxic to HepG2 cells. There was a steep dose response relationship, and the effective dose (LD50) was 1.2 microCi (480 rads). The cytotoxic effects of I-131-lipiodol were associated with pleomorphism of HepG2 cells, an increase in cell size and nuclear-cytoplasmic ratio, an increase in the size and number of nuclei, and vacuolation of the cytoplasm around the nuclear regions. Multiple nucleoli, fragmentation and segregation and ring shaped changes of nucleoli were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)