Michael R. Koch

Divergent effects of cyanate on amino acid and phosphate uptake by liver and hepatoma

The uptake of alpha-aminoiso[3H]butyric acid and 32Pi was observed to be inhibited by sodium cyanate in transplanted hepatomas but was increased in the livers of the tumor bearing rats. Incorporation of 32Pi into macromolecules in hepatomas was also inhibited by cyanate. Treatment with this drug did not influence circulating concentrations of isotope-labeled materials. There were relatively small effects on uptake of 36Cl- in cyanate-treated rats and the action was not tissue specific. The data were compatible with an inhibitory effect of cyanate on active transport in hepatomas which was not seen under the same conditions in host liver.

Stimulatory effect of dimethylsulfoxide on [3H]thymidine incorporation into DNA in Novikoff hepatoma cells.

Abstract 1. 1. [3H]thymidine incorporation into DNA of Novikoff hepatoma cells increased over 400% in cells preincubated with 2.5% of dimethysulfoxide (DMSO). 2. 2. The addition of 2.5% DMSO directly to the incubation mixture or preincubation with 20% DMSO inhibited [3H]thymidine incorporation. 3. 3. DMSO also stimulated [3H]uridine incorporation into RNA but not [3H]amino acid incorporation into protein. 4. 4. The stimulatory effect of low histone concentrations on [3H]thymidine incorporation was not observed following preincubation with DMSO.

Decreased incorporation of phosphate and amino acids into low-solubility, nuclear proteins in rapidly growing hepatomas

Abstract 1. 1. The incorporation of 32 P-phosphate and 3 H-amino acids was studied in nuclear protein fractions of normal and neoplastic liver. 2. 2. The most marked change in hepatomas was a decreased incorporation of isotope into a low solubility fraction of non-histone proteins in rapidly growing tumors. 3. 3. The phosphate content of this fraction was lower in Morris hepatomas 9618A 2 and 7777 than host livers. 4. 4. Significant decreases were not seen in slowly growing hepatomas and regenerating rat liver.

Inhibition of macromolecular synthesis in tumors by L-1-tosylamido-2-phenylethyl chloromethyl ketone

Abstract L-1-tosylamido-2-phenylethyl chloromethyl ketone was observed to inhibit the incorporation of [ 3 H] amino acids into protein and [ 3 H] thymidine incorporation into DNA in Novikoff hepatoma ascites cells in vitro Similar effects were seen with several Morris hepatomas and a transplanted colon tumor in rats, and were accompanied by decreased uptake of isotope into acid soluble tissue fractions. Under the same conditions, there was no significant inhibition in regenerating liver and there was an increased uptake of [ 3 H] amino acids in the livers of normal and tumor bearing rats.