Ehrlich ascites carcinoma

About: Ehrlich ascites carcinoma is a research topic. Over the lifetime, 1925 publications have been published within this topic receiving 32987 citations.

Studies on Fluorinated Pyrimidines II. Effects on Transplanted Tumors

Abstract: 1. The activity of a new series of fluorinated pyrimidines has been screened against several transplanted tumors. 2. In general, the activity of 5-fluorouracil was greater than that of 5-fluoroorotic acid. 5-Fluorocytosine, 2-methylmercapto-5-fluorouracil, and 2-thio-5-fluorouracil did not have appreciable tumor-inhibitory activity. 3. The toxicity of 5-fluorouracil was characterized by delayed deaths, hematopoietic depression, diarrhea, weight loss, and hemorrhages in the lungs and intestines. 4. These compounds acted as tumor growthinhibitors rather than as carcinolytic substances. 5. The activity of 5-fluorouracil was considerably greater than that of 6-mercaptopurine and OPSPA on the Ehrlich ascites carcinoma, Novikoff hepatoma, and L1210 leukemia, and less than either or both of those compounds on Sarcoma 180, 755 and E 0771 mammary adenocarcinomas, Sarcoma A-1, Flexner-Jobling carcinoma, Walker 256 carcinosarcoma, and Yoshida ascites sarcoma. 6. Some potentiation of activity against the solid tumors has been obtained when 5-fluorouracil was combined with 6-mercaptopurine, 5-bromouracil, or x-ray treatment.

Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones.

Abstract: The cytotoxicity of the clinically important antineoplastic quinones doxorubicin, mitomycin C, and diaziridinylbenzoquinone for the Ehrlich ascites carcinoma was significantly reduced or abolished by the antioxidant enzymes catalase and superoxide dismutase, the hydroxyl radical scavengers dimethyl sulfoxide, diethylurea, and thiourea, and the iron chelators deferoxamine, 2,2-bipyridine, and diethylenetriaminepentaacetic acid. However, tumor cell killing by 5-iminodaunorubicin, a doxorubicin analog with a modified quinone function that prohibits oxidation-reduction cycling, was not ameliorated by any of the free radical scavengers tested. Furthermore, treatment of intact tumor cells with doxorubicin, mitomycin C, and diaziridinylbenzoquinone but not 5-iminodaunorubicin generated the hydroxyl radical, or a related chemical oxidant, in vitro in a process that required hydrogen peroxide, iron, and intact tumor cells. These results suggest that drug-induced hydrogen peroxide and hydroxyl radical production may play a role in the antineoplastic action of redox active anticancer quinones.

Studies in a Tumor Spectrum III. The Effect of Phosphoramides on the Growth of a Variety of Mouse and Rat Tumors

Abstract: Summary 1.The effects of diethylene phosphoramide (DEPA), triethylene phosphoramide (TEPA), and triethylene thiophosphoramide (TSPA) have been tested against a spectrum of eighteen tumors of the mouse, five tumors of the rat, and three ascites tumors of the mouse. 2.Daily maximum tolerated doses of 6 mg/kg of TEPA in mice had a destructive effect on Carcinoma 1025, Ridgway osteogenic sarcoma, and Andervont hepatoma; a marked inhibitory effect on Miyono adenocarcinoma and Gardner lymphosarcoma; a moderate inhibitory effect on Sarcoma 180, Adenocarcinoma E 0771, Ehrlich carcinoma, Grand epidermoid carcinoma, Wagner osteogenic sarcoma, Lewis bladder carcinoma, and Lewis lung carcinoma; a slight inhibitory effect on Sarcoma MA 387, Bashford carcinoma 63, and Harding-Passey melanoma, but no effect on Sarcoma T 241. 3.Daily maximum tolerated doses of 4 mg/kg of TSPA in mice had a destructive effect on Carcinoma 1025, Ridgway osteogenic sarcoma, Gardner lymphosarcoma, and Andervont hepatoma; a marked inhibitory effect on Adenocarcinoma E 0771 and Bashford carcinoma 63; a moderate inhibitory effect on Sarcoma 180, Miyono adenocarcinoma, Ehrlich carcinoma, Grand epidermoid carcinoma, Wagner osteogenic sarcoma, Harding-Passey melanoma, Lewis bladder carcinoma, and Lewis lung carcinoma, and a slight inhibitory effect on Sarcoma T 241, Sarcoma MA 387, Patterson lymphosarcoma, and Mecca lymphosarcoma. 4.The effects of TEPA and TSPA on these eighteen mouse tumors were generally similar, and these compounds were far more effective than DEPA. 5.Both TEPA and TSPA had a marked inhibitory effect upon the development of Ehrlich ascites carcinoma and Krebs 2 ascites carcinoma, but only a slight inhibitory effect on Sarcoma 180 ascites tumor. DEPA had relatively no effect on these three ascites tumors. 6.The growth of spontaneous mammary adenocarcinomas in Swiss albino mice was stopped by repeated injections of TSPA, but there was no significant increase in complete tumor regression over the controls. 7.Daily doses of 1 mg/kg of DEPA, 1 mg/kg of TEPA, and 2 mg/kg of TSPA in rats had a destructive effect on 1-day-old implants of Flexner-Jobling carcinoma, Walker carcinosarcoma 256, Sarcoma R 39, and Jensen sarcoma, but no effect on Murphy-Sturm lymphosarcoma. 8.Complete regression was obtained in large numbers of certain well established 7-day-old mouse and rat tumors by administration of seven daily doses of DEPA, TEPA, and TSPA. For rats, daily doses of 1-2.5 mg/kg of DEPA gave 80 per cent regressions for Flexner-Jobling carcinoma, 65 per cent for Sarcoma R 39, and 80 per cent for Jensen sarcoma. For mice, daily doses of 6 mg/kg of TEPA gave 82 per cent regressions for Carcinoma 1025, 83 per cent for Ridgway osteogenic sarcoma, and 80 per cent for Gardner lymphosarcoma. Similarly, for rats, daily doses of 1 mg/kg of TEPA gave 73 per cent regressions for Flexner-Jobling carcinoma, 93 per cent for Sarcoma R 39, and 75 per cent for Jensen sarcoma. Similarly, for mice, daily doses of 4 mg/kg of TSPA gave 83 per cent regressions for Carcinoma 1025, 78 per cent for Ridgway osteogenic sarcoma, and 70 per cent for Gardner lymphosarcoma. For rats, daily doses of 2 mg/kg gave 80 per cent regressions for Flexner-Jobling carcinoma, 60 per cent for Walker carcinosarcoma 256, and 86 per cent for Jensen sarcoma.

Studies on fluorinated pyrimidines. III. The metabolism of 5-fluorouracil-2-C14 and 5-fluoroorotic-2-C14 acid in vivo.

Abstract: Summary 1.The excretion, distribution, and metabolism of 5-fluorouracil-2-C 14 and 5-Fluoroorotic-2-C 14 acid have been studied in normal and tumor-bearing mice and in a human cancer patient. 2.Both compounds were rapidly excreted in the urine. 5-Fluorouracil was excreted unchanged shortly after injection. At later times several as yet uncharacterized metabolites were excreted. The radiocarbon appeared much more extentively in the respiratory carbon dioxide following 5-fluorouracil injection than after 5-fluoroorotic acid administration. 3.At all times after intraperitoneal injection of 5-fluorouracil into mice bearing Sarcoma 180, a higher specific activity was found in the tumor than in all other tissues investigated. In the cancer patient the tumor biopsy had a higher specific activity than surrounding skin, muscle, fat, and a liver biopsy. No selective localization of radioactivity in tumor occurred with labeled 5 fluoroorotic acid. 4.5-Fluorouracil and 5-fluoroorotic acid were converted into acid-soluble fluorouridine nucleotides at the mono-, di-, and triphosphate levels, and were incorporated into RNA, but not DNA, in mouse liver, spleen, Sarcoma 180, Ehrlich ascites carcinoma, and a human metastatic carcinoma. The incorporation into RNA at most represented a quantity equivalent to 6 per cent of the uracil content. 5-Fluoroorotic acid was decarboxylated and was present in the RNA as 5-fluorouracil in nucleotide linkage, most probably distributed randomly throughout the macromolecule.