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Abnormal Cholesterol Uptake, Storage, and Synthesis in the Livers of 2-Acetylaminofluorene-fed Rats¹

Departments of Oncology and Pathology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706

Rat livers were tested for both rate of cholesterol synthesis and uptake of a p.o. dose of cholesterol-³H after rats were fed 0.06% 2-acetylaminofluorene (AAF) for either 1 or 2 weeks. For the 2 days prior to the assay, all rats also received 5% cholesterol in the diet.

In the control group, the high-cholesterol diet caused almost complete inhibition of cholesterol synthesis, but after AAF treatment the levels of cholesterol synthesis were markedly higher, with considerable variation between individual rats. Uptake of cholesterol-³H given p.o. was significantly lower in the AAF group and was also variable, but there was no correlation with sterol synthesis, indicating that impairment of cholesterol uptake is not the critical factor in loss of control. However, liver cholesterol levels in the AAF-fed rats were significantly lower than those in control animals, and there was a highly significant inverse correlation between liver cholesterol levels and sterol synthesis. Therefore, the lack of regulation of cholesterol synthesis induced by AAF appears to be a result of a defect in intracellular storage of cholesterol rather than defective uptake.

¹ Supported in part by NIH General Research Support Grant G-374-6, National Cancer Institute Grant CA-07175, and American Cancer Society Grant E-588.

² Employed in this investigation during the tenure of a Damon Runyon Cancer Research Fellowship. Present address: Department of Experimental Pathology, John Curtin School of Experimental Medicine, Australian National University, Canberra, A. C. T., 2601, Australia.

Received 11/14/72. Accepted 3/ 9/73.