Through our study on morphologic changes occurring in hepatocellular carcinomas (HCCs) treated with trans-arterial chemo-embolization(TAE), we noticed that significant differences of morphologic features and proliferative activity existed between HCCs before and after TAE. In order to investigate whether such changes could be explained by adriamycin, we performed in vitro administration of adriamycin to HCC cell lines. Using three HCC cell lines(SNU-354, SNU-398, SNU-449) established in our hospital, we added 20 ￥ig of adriamycin to the culture dishes at the beginning and doubled the dose every three days. Three cell lines showed different drug susceptibility and SNU-398 was the most sensitive one. Initial morphologic changes were cellular edema and clearing. Damaged cells showed decrease of the size of cytoplasm and the cell processes became thinner and longer. Ultrastructurally, treated cells had small cytoplasm and scanty organelles. Some of the cells contained many lipid vacuoles. Nuclear chromatins demonstrated clumping tendency in the treated cell lines. Adriamycin caused shortening of doubling time in SNU-449, which was statistically not significant. No difference of ploidy was seen between untreated and treated cell lines. In summary, the morphological changes of hepatocellular carcinoma cell line induced by adriamycin in vitro is not exactly the same pattern as that of in vivo chemo-embolization procedure. The above findings suggested that the morphological changes of hepatocellular carcinoma induced by adriamycin chemo-embolization was induced not only by chemotherapeutic drug but also by accompanying environmental factors such as hypoxic insult.
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