Folic acid metabolism in Rauscher murine leukemia and effect of methotrexate on the blood picture.

Folic acid contents of plasma, whole blood, liver and spleen in Rauscher leukemic mice were estimated. Plasma and liver folate in the leukemic mice was lower than that of normal mice, suggesting that folic acid was deficient in Rauscher leukemia. Folic acid contents in whole blood and spleen were even higher in the leukemic mice than those in normal mice. Clearance study by injecting folic acid intravenously into leukemic mice showed faster disappearance of folic acid from the circulating blood, suggesting that folic acid demand of Rauscher leukemia is increased. Methotrexate administered shortly after inoculation of the virus did not prevent Rauscher leukemia. But anemia, reticulocytosis and erythroblastosis, which are commonly seen 3-4 weeks later in leukemic controls, were not marked as compared with controls. It can be concluded that the requirement of folic acid is greater in Rauscher leukemia than in controls, and methotrexate is effective for preventing hematological changes commonly seen in this type of leukemias. ∗PMID: 4281996 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 28, 353-359 (1974) FOLIC ACID METABOLISM IN RAUSCHER MURINE LEUKEMIA AND EFFECT OF METHOTREXATE ON THE BLOOD PICTURE Hirokuni T AGUCHI, Hiroshi SANADA Central Laboratories, Okayama University Medical School, Okayama, Japan Toshio HASEI, Koichi HARA, Ichiro MIZUKAWA, Tatsuo SEZAKI, Shozo IRINO, Ichiro IWASAKI and Kiyoshi HIRAKI Department of Internal Medicine, Okayama University Medical School, Okayama, Japan Receivedfor publication, March 29, 1974 Abstract: Folic acid contents of plasma, whole blood, liver and spleen in Rauscher leukemic mice were estimated. Plasma and liver folate in the leukemic mice was lower than that of normal mice, suggesting that folic acid was deficient in Rauscher leukemia. Folic acid contents in whole blood and spleen were even higher in the leukemic mice than those in normal mice. Clearance study by injecting folic acid intravenously into leukemic mice showed faster disappearance of folic acid from the circulating blood, suggesting that folic acid demand of Rauscher leukemia is increased. Methotrexate administered shortly after inoculation of the virus did not prevent Rauscher leukemia. But anemia, reticulocytosis and erythroblastosis, which are commonly seen 3-4 weeks later in leukemic controls, were not marked as compared with controls. It can be concluded that the requirement of folic acid is greater in Rauscher leukemia than in controls, and methotrexate is effective for preventing hematological changes commonly seen in this type of leukemias. Folic acid contents of plasma, whole blood, liver and spleen in Rauscher leukemic mice were estimated. Plasma and liver folate in the leukemic mice was lower than that of normal mice, suggesting that folic acid was deficient in Rauscher leukemia. Folic acid contents in whole blood and spleen were even higher in the leukemic mice than those in normal mice. Clearance study by injecting folic acid intravenously into leukemic mice showed faster disappearance of folic acid from the circulating blood, suggesting that folic acid demand of Rauscher leukemia is increased. Methotrexate administered shortly after inoculation of the virus did not prevent Rauscher leukemia. But anemia, reticulocytosis and erythroblastosis, which are commonly seen 3-4 weeks later in leukemic controls, were not marked as compared with controls. It can be concluded that the requirement of folic acid is greater in Rauscher leukemia than in controls, and methotrexate is effective for preventing hematological changes commonly seen in this type of leukemias. Folic acid is a cofactor of thymidilate synthetase during the synthesis of DNA (1), and it plays an important role in cell division through its action (2) in the DNA synthesis. Its requirement increases in malignant neoplasms and leukemias, because cell division is accelerated in such diseases (3). The fact that a folic acid antagonist, amethopterin (methotrexate, MTX) is effective for some leukemias and choriocarcinoma (4) suggests that folic acid metabolism is accelerated in these diseases. Prolongation of the survival time in the animals with leukemias by MTX has been reported (5) (6). But folic acid metabolism in experimental leukemias of mice is little known except a report of silverman et al. (7) ; and SoTOBAYASHI (8) who studied folic acid metabolism in Walker sarcoma. In the present paper, folic acid metabolism and effects of MTX are examined in Rauscher leukemic mice to study the relationship between folate