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Free Amino Acids in Growing and Regressing Ascites Cell Tumors: Host Resistance and Chemical Agents^*

Eugene Roberts, K. Kano Tanaka, T. Tanaka and Daisy G. Simonsen

( Departments of Biochemistry and Cytology, Medical Research Institute, City of Hope Medical Center, Duarte, Calif.)

1. A description was given of the cytological characteristics of Yoshida ascites tumor cells and of the content of ninhydrin-reactive constituents detected on two-dimensional paper chromatograms prepared from extracts of the cells and ascitic fluid at various times after transplantation into a susceptible rat (J strain), in which the tumor grew progressively and killed the animal in 14 days, and into a resistant rat (Wistar), in which the tumor grew initially but regressed completely within 8 days. At all times after transplantation the content of free or easily extractable glutamine was higher in the cells grown in the resistant rat. The chemical findings generally were similar to those observed previously in comparable experiments with mice bearing the C1498 leukemia.

2. Detailed results were given of the sequential changes in the cytological features of the cells and of amino acid patterns of extracts of the cells and fluid of the Yoshida sarcoma in rats after the administration of sarkomycin, nitromin, or crude podophyllin and of the Ehrlich ascites tumor in mice after the injection of sarkomycin. Patterns of cytoplasmic and nuclear damage produced by sarkomycin and podophyllin were similar to each other but differed from that observed with nitromin, an agent whose initial action is primarily upon the nucleus. All of the above substances produced increases in the content of free glutamine in the tumor cells and ascitic fluid, with sarkomycin showing the most marked increase most rapidly. Other changes in ninhydrin-reactive constituents also were described.

3. A consideration of both the cytological and chemical changes produced by sarkomycin suggested that the glutamine which appears rapidly after treatment may be intracellular in origin. An experiment with DL-glutamine-2-C¹⁴ showed that treatment with sarkomycin in vivo did not destroy the ability of Yoshida tumor cells to take up labeled glutamine in vitro rapidly and to convert it to glutamic acid.

4. A similarity of certain aspects of the molecular models of sarkomycin and glutamine suggested the possibility that sarkomycin might be interfering with some phase of utilization of glutamine in the susceptible cells.

^* This investigation was supported by research grant C-2568 from the National Cancer Institute, United States Public Health Service.

Present address, Department of Zoology, Hokkaido University, Japan.

Received 6/18/56.