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A new deoxyuridine-5'-triphosphatase in Yoshida sarcoma cells involved in deoxyuridine 5'-triphosphate metabolism.

A magnesium-independent deoxyuridine-5'-triphosphatase was found in Yoshida sarcoma cells but not in normal rat liver. The phosphatase is specific for deoxyuridine 5'-diphosphate and deoxyuridine triphosphate, and its Km for deoxyuridine triphosphate is 2.7 X 10(-7) M. The enzyme was not inhibited by fluoride and required no divalent cations. Thus it differs from known nucleotide phosphatases. Deoxyuridine monophosphokinase, which is detectable in a crude extract of normal rat liver, could not be detected in an extract of Yoshida sarcoma cells. However, with hydroxylapatite column chromatography of the extract, a deoxyuridine 5'-monophosphate kinase activity as high as that in normal rat liver was found in fractions separated from the phosphatase activity. Thus the absence of detectable deoxyuridine 5'-monophosphate kinase activity in the crude extract of Yoshida sarcoma cells is due to the presence of this nucleotide phosphatase.

Animals↗

Antitumor activity of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(4-methyl-cyclohexyl)-1-nitrosourea (MeCCNU) on Yoshida sarcoma ascites cells implanted into the colon wall of rats.

Three thousand Yoshida sarcoma cells were inoculated into the wall of the descending colon of each of 120 male Sprague-Dawley rats. On day 8 after the tumor implantation, the animals were at random divided into four groups of 30 rats each. The effect of cyclophosphamide (70 mg/kg), BCNU (25 mg/kg), and methyl-CCNU (45 mg/kg) after single i.p. application was investigated. The Yoshida sarcoma transplanted into the colon is sensitive to all three chemotherapeutic drugs. At the doses given cyclophosphamide showed the best results. The two nitrosoureas had a comparable antitumor activity but methyl-CCNU showed a more distinct toxic effect. The introduction of this model for testing new cytostatics in animal experiments is discussed.

Animals↗

The curative action of hexamethylmelamine on intramuscularly or intracerebrally implanted Yoshida sarcoma.

Curative effects of hexamethylmelamine (HMM, NSC 13875) against intramuscularly or intracerebrally implanted Yoshida sarcoma depend on the schedules. A twice daily oral administration over a 2-week period showed a significant chemotherapeutic advantage over a single daily administration. The observed curative effect depends on the tumour site and on its mass. The Yoshida sarcoma seems to be one of the most suitable test models for HMM or related derivatives.

Altretamine↗

A comparative pharmacology study between the intracolonic and oral routes of 5-FU administration in a colon cancer-bearing Yoshida sarcoma rat model.

We prepared a colon cancer-bearing Yoshida sarcoma rat model to examine the dose-response relationship of antitumor activity of intracolonically or orally administered 5-fluorouracil (5-FU; 45, 30, 20, 13, and 8 mg/kg). At doses of > or =20 mg/kg and > or =30 mg/kg, the 5-FU intracolonic and oral administration groups each showed a statistically significant difference in antitumor activity against the control group (P<0.05, Williams' test). A statistically significant dose-response relationship was noted in the two routes of administration, with an ED(50) value of 29 mg/kg. White blood cell count tended to decrease at high doses when 5-FU was administered intracolonically and showed a statistically significant decrease at doses of > or =30 mg/kg when 5-FU was administered orally. Regarding the time-course of body weight, even the 5-FU highest dose (45 mg/kg) intracolonic administration group showed no inhibited body weight increase compared to the control group. However, the 5-FU (> or =20 mg/kg) oral administration groups showed a statistically significant difference in body weight increase against the control group. These facts suggested that the intracolonic administration of 5-FU, while exhibiting more potent antitumor activity than that observed in oral administration, allows an extensive reduction in its toxicities compared to oral administration.

Administration, Oral↗

Metastasis formation of Yoshida sarcoma heterotransplanted in adult golden hamsters treated with anti-hamster thymocyte serum.

Growth of Yoshida sarcoma cells heterotransplanted in adult golden hamsters treated with antithymocyte serum was investigated. Control animals were grafted with or without hydrocoritisone conditioning. In the antithymocyte serum-treated group, tumors were produced in cheek pouches and grew progressively in size until Day 21 with no sign of regression. Little host reaction was noticed histologically around the tumor grafts throughout the course. Distant metastases were revealed at autopsy in 9 of 12 animals from Day 14 of inoculation on, and all the experimental animals died by Day 23. Six of the 9 hamsters with metastases died of tumor. By means of the back-transplantation test, the metastatic tumor cells were shown to be consistent with Yoshida sarcoma cells. In hydrocortisone-treated and untreated groups, the tumor size reached a maximum on Day 21 and Day 5, respectively, and then regression followed. No metastasis was detected in either control group.

Animals↗