, Volume 412, Issue 6, pp 595-606

Comparative morphology and tumourigenicity of human hepatocellular carcinoma cell lines in athymic rats and mice

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Four human hepatoma cell lines PLC/PRF/5, Hep G2, Sk-Hep 1 and Mahlavu were inoculated subcutaneously into athymic Balb/c nude mice and N/NIH outbred nude rats, producing well encapsulated tumours. The 4 hepatoma tumour types in the athymic rodents differ morphologically. PLC/PRF/5 and Hep G2 cells are well differentiated polygonal cells which resemble normal hepatocytes. Tumour arrangement is characterized by solid masses and trabeculae while stromal support is minimal. In contrast, Mahlavu and Sk-Hep 1 tumours have a sarcomatous appearance and consist of spindle shaped cells arranged in solid masses with a rich stromal support. Tumourigenicity of hepatoma cells in the athymic rodents was dependent on injected cell type, inoculation density, relative immunocompetence of the host and the species of animals used. In nude mice, Sk-Hep 1 cells were the most tumourigenic, while Hep G2 cells were tumourigenic only at very high inoculation densities. In nude rats, which were more resistant to tumour formation, PLC/PRF/5 cells were the most tumourigenic. Pre-treatment of athymic mice and rats with total body irradiation resulted in enhanced tumourigenicity for all hepatoma cell lines tested. This was manifested as increased “take” rates, a decreased latency from tumour cell injection to tumour detection, increased tumour weight, and for PLC/PRF/5 cells an increased invasiveness to adjacent body cavities. Furthermore, following irradiation, the minimal number of injected cells required to produce subcutaneous tumours was markedly reduced in both animal species, regardless of tumour cell type. The protocols described enable the reproduceable growth of human hepatoma tumours in athymic rodents.