DELETION OF THE CHOLESTEROL-NEGATIVE FEEDBACK SYSTEM IN LIVER TUMORS.

This study represents an attempt to determine whether the cholesterol feedback system, which is characteristic of normal liver, is retained when hepatic tissue becomes malignant. In the mouse hepatoma BW 7756, the Morris rat hepatoma 5123-t.c., and in one relatively well differentiated human hepatoma cholesterol synthesis was found to proceed at significant rates, indicating that the enzymatic mechanism for cholesterogenesis is present in these tumors. Nonetheless, each of these three hepatomas completely lacked the cholesterol-negative feedback control mechanism. The presence of a subcutaneous hepatoma was found to have no influence on the normal feedback system in the liver of the tumor-bearing animal. Finally, it was shown that regenerating livers of both the mouse and the rat are capable of normal feedback response, a finding which suggests that the absence of this feedback system may be secondary to the tissue malignancy per se rather than to rapid cellular proliferation. The observation that cholesterol feedback control is lost in hepatomas derived from three different species offers the first direct experimental support for the suggestion that there may be a relationship between the deletion of feedback control and carcinogenesis.

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