Carcinogenesis In Tissue Culture. XIV. Malignant Transformation of Rat Liver Parenchymal Cells Treated With 4-Nitroquinoline 1-Oxide In Tissue Culture234

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Abstract
A diploid strain of liver parenchymal cells from a normal inbred rat was treated in culture with 3.3 × 10-6M 4-nitroquinoline 1-oxide (4NQO) at 37° C one to several times, each time for 30 minutes. In each of 5 experiments the treated cells became malignant. In 1 experiment, the cells were transformed by only 1 treatment: They were backtransplanted about 3.5 months after the treatment intraperitoneally into 2 suckling rats, one of which died with tumor after 3.6 months. Repeated 4NQO treatments did not shorten the lifespans of the transplanted animals, except in 1 study. Tumor ascites consisted of isolated single cells and various sizes of cell clumps, whose morphology closely resembled that of other transplantable rat ascites hepatoma lines. The tumor cells in the ascites could grow in other rats as well as in tissue culture. Tumor nodules produced on the peritoneum were shown histologically to contain both sarcomatous and carcinomatous cells. Continuous cinemicrography for more than 6 months revealed no marked change in static morphology of the treated cells but did show a loss of intercellular adhesiveness, suggesting some change in the cell membrane. The transformed strains lost 1 or 2 chromosomes in the modal number, and they did not agglutinate with concanavalin A. The untreated control cells did not produce tumors on backtransplantation at the 4-month stage, when 4NQO-treated cells were confirmed to be malignant in 4 of 5 series, but they underwent spontaneous transformation by the 17th month.

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