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Effects of Cyanate on the Distribution of Isotope-labeled H₂O and Extracellular Markers in Rat Liver and Tumors¹

Department of Biochemistry, College of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103

Previous work has shown that administration of sodium cyanate inhibits the uptake of several metabolites in tumors under conditions in which there is generally no inhibition in normal tissues of the rat. In the present work, it was found that cyanate treatment inhibits the distribution of ³H₂O, [³H]methoxyinulin, and [¹⁴C]sucrose in rats with greater effects in the tumors than the normal tissues examined. Tumor-bearing rats received i.p. injections of sodium cyanate (250 mg/kg body weight). After 60 min, the rats received s.c. injections of ³H₂O. Treatment with cyanate decreased the radioactivity in blood and liver, but greater effects were seen in five transplanted tumors (LK1 colon tumor and Morris hepatomas 5123C, 7288CTC, 7777, and 9618A₂). At 10 min after injection of ³H₂O, the mean radioactivities in tumors of cyanate-treated rats were 11 to 23% of control values and in some tumors were still less than in controls at 60 min after isotope injection. Evidence was obtained that the action of cyanate was not due to osmotic effects or loss of water from the tissues. The distribution of the extracellular markers [³H]methoxyinulin and [¹⁴C]sucrose was also decreased in hepatomas in cyanate-treated rats. The data do not exclude effects on membrane permeability but suggested that cyanate decreased circulation in the tumors.

¹ Supported in part by Grant CA-16274 from the National Cancer Institute.

Received 7/ 1/81. Accepted 9/10/81.