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Effects of Hydroxyethylation on the Uptake of Rat Albumin by Tissues of the Tumor-bearing Rat^*

Wesley C. Starbuck and Harris Busch

( Department of Pharmacology, Baylor University College of Medicine, Houston, Texas)

To test the feasibility of using plasma albumin as a carrier of cytotoxic agents into tumor cells, experiments were carried out to determine the effect of hydroxyethylation on the uptake of albumin into the tumor and other tissues of the tumor-bearing rat. Three hours after injection of either (a) labeled, unmodified albumin, (b) labeled albumin which was hydroxyethylated for 1 or 3 hours, or (c) albumin hydroxyethylated for 1 hour with ethylene-1,2-C¹⁴ oxide, the specific activities of the intracellular proteins of the tumor were greater than the corresponding values for the proteins of the liver, kidney, spleen, and lung. Following the injection of labeled albumin which had been treated with ethylene oxide for 6 or 24 hours, the specific activities of the proteins of the whole homogenate, mitochondria, and microsomes of the tumor were only slightly greater than the corresponding values following the injection of labeled, unmodified albumin. However, a large increase in the specific activities of the proteins of the liver, kidney, spleen, and lung was observed; the values obtained were from 2.7 to 6.5 times greater than the values obtained following the injection of labeled, unmodified albumin. These studies provide evidence that albumin, when modified to a limited extent, may be of value as an agent for carrying cytotoxic groups into neoplastic cells.

^* Supported by grants from the American Cancer Society, the U.S. Public Health Service, and the Jane Coffin Childs Fund.

Predoctoral Trainee of the U.S. Public Health Service.

Received 6/ 1/62.