Effect of glucuronic acid on benzpyrene-induced skin cancer.

Abstract

1. One mg. of pyruvate-2-C14 containing 6 µc. of radioactivity was injected intravenously into rats bearing Flexner-Jobling carcinomas, Walker 256 carcinosarcomas, or Jensen sarcomas. The experiments were terminated 15 seconds to 8 minutes after the injection. The half-time for absorption of the isotope from the blood was 15 seconds. 2. In nontumor tissues, 30–80 per cent of the isotope was transferred to the amino acids, alanine, glutamic acid, and aspartic acid, by 1 minute after the injection of the tracer. The rates of increase of total isotope in these amino acids exceeded the values for blood, and a steady state for the percentage of total isotope in these amino acids was reached by 3 minutes after injection of the pyruvate-2-C14. 3. Marked individual differences were noted, among the tissues, in the amino acids labeled. In liver, testis, muscle, and intestine, labeling of alanine was greatest and accounted for 27–32 percent of the total isotope in the tissue 1 minute after injection of the pyruvate-2-C14. In brain, heart, and kidney, glutamic acid contained 45–65 per cent of the total isotope, and a relatively small percentage was found in alanine. 4. The tumors were unique in that labeling of amino acids was not significantly different from that in the blood. Inasmuch as the rates of increase in the percentage of isotope in amino acids were the same as that of the blood, the data suggest that there was little or no transfer of isotope from pyruvate-2-C14 to amino acids by the tumors. 5. At early time points, a considerable percentage of isotope was found in lactate in most tissues, but diminished to a range of 3–20 per cent for nontumor tissues by 8 minutes after injection of the pyruvate-2-C14. In the tumors, 50 per cent of the total isotope remained in lactate 8 minutes after the injection of the tracer. 6. Small percentages of isotope were found in succinate, a neutral fraction, and CO2 at early time points. Following the introduction of a malonate block, the specific activity of succinate in nontumor tissues was 300–9,000 counts/min/µm, while that of tumors was zero. 7. These experiments indicate that the primary metabolic pathways of pyruvate-2-C14 lead to the amino acids, alanine, glutamic acid, and aspartic acid, as well as lactate in the nontumor tissues studied. In the tumors, the amination reactions were not significant.