Transformation of isolated rat hepatocytes with simian virus 40.

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Abstract
Rat hepatocytes were transformed by SV40. Hepatocytes from 2 different strains of rats and a temperature-sensitive mutant (SV40tsA1609), and wild-type virus were used. In all cases, transformed cells arose from .apprx. 50% of the cultures containing hepatocytes on collagen gels or a collagen gel-nylon mesh substratum. Cells did not proliferate in mock-infected cultures. SV40-transformed hepatocytes were epithelial in morphology, retained large numbers of mitochondria, acquired an increased nucleus to cytoplasm ratio and contained cytoplasmic vacuoles. Evidence that these cells were transformed by SV40 came from the findings that transformants were 100% positive for SV40 tumor antigen expression, and that SV40 was rescued when transformed hepatocytes were fused with monkey cells. All SV40-transformed cell lines tested formed clones in soft agarose. Several cell lines transformed by SV40tsA1609 were temperature dependent for colony formation on plastic dishes. Transformants were diverse in the expression of chracteristic liver gene functions. Of 8 cell lines tested, 1 secreted 24% of total protein as albumin, whcih was comparable to albumin production by freshly plated hepatocytes; 2 other cell lines produced 4.2 and 5.7%, respectively. Tyrosine aminotransferase activity was present in 5 cell lines tested but was inducible by dexamethasone treatment in only 2. Adult, nonproliferating rat hepatocytes are apparently competent for virus transformation.