Journal ArticleDOI
Biochemical Basis for Fluorouracil Neurotoxicity: The Role of Krebs Cycle Inhibition by Fluoroacetate
Harold Koenig,Abdussamad Patel +1 more
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TLDR
F fluorouracil, like other agents which block DNA synthesis, is toxic chiefly to rapidly dividing normal cells, ie, epithelial cells of the alimentary tract and hematopoietic elements of bone marrow and lymphoid tissues.Abstract:
THE PYRIMIDINE analog fluorouracil has been used extensively in the chemotherapy of malignant neoplasms since its introduction by Heidelberger and associates in 1957. 1 The carcinostatic property of fluorouracil seems to be due to anabolic reactions. Although fluorouracil is readily converted to acid-soluble fluorouracil nucleotides, undergoes incorporation into RNA, and interferes with RNA synthesis in mammalian tissues and tumor cells, 2 its major chemotherapeutic and toxic effects are attributable to an interference with DNA synthesis and cell division. The latter effect is due to inhibition of thymidylate synthetase, the enzyme which catalyzes the conversion of deoxyuridylate of thymidylate, by the fluorouracil derivative fluorodeoxyuridylate (FUDR). 2 Thus fluorouracil, like other agents which block DNA synthesis, is toxic chiefly to rapidly dividing normal cells, ie, epithelial cells of the alimentary tract and hematopoietic elements of bone marrow and lymphoid tissues. 3-5 Recently, Riehl and Brown 6 described an acute neurological disorderread more
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Neurological complications of 5-fluorouracil chemotherapy: Case report and review of the literature
TL;DR: The two patients presented demonstrate two manifestations of 5-FU neurotoxicity, namely a cerebellar syndrome in association with global motor weakness and bulbar palsy, and a bilateral third cranial (oculomotor) nerve palsy.
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NEUROTOXIC EFFECTS OF α-FLUORO-β-ALANINE (FBAL) AND FLUOROACETIC ACID (FA) ON DOGS
TL;DR: FBAL is one of the main substances that cause neurotoxic signs and neuropathological changes in dogs intoxicated by 5-FU or its masked compounds, and FA might be considered to be a causative factor in addition to FBAL.
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Modulation of 5-fluorouracil activation of toll-like/MyD88/NF-κB/MAPK pathway by Saccharomyces boulardii CNCM I-745 probiotic.
Priscilla F. C. Justino,Álvaro Xavier Franco,Rodolphe Pontier-Bres,Carlos Eduardo da Silva Monteiro,André Luiz dos Reis Barbosa,Marcellus H.L.P. Souza,Dorota Czerucka,Pedro Marcos Gomes Soares +7 more
TL;DR: Toll-like/MyD88/NF-κB/MAPK pathway are activated during intestinal mucositis and their modulation by S.b suggests a novel and valuable therapeutic strategy for intestinal inflammation.
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The Effect of Dihydropyrimidine Dehydrogenase Deficiency on Outcomes with Fluorouracil
TL;DR: The recognition that DPD deficiency increases toxicity has lead to the suggestion that genotypic or phenotypic assessment of DPD status prior to initiating fluorouracil may help predict outcomes, and further study is needed before the best means of optimising fluoroursacil treatment is determined.
References
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Fluorinated Pyrimidines, A New Class of Tumour-Inhibitory Compounds
Charles Heidelberger,N. K. Chaudhuri,Peter B. Danneberg,Dorothy Mooren,Lois Griesbach,Robert Duschinsky,R. J. Schnitzer,E. Pleven,J. Scheiner +8 more
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Studies on Fluorinated Pyrimidines II. Effects on Transplanted Tumors
Charles Heidelberger,Lois Griesbach,Betty Jo Montag,Dorothy Mooren,Olivia Cruz,R. J. Schnitzer,E. Grunberg +6 more
TL;DR: The activity of a new series of fluorinated pyrimidines has been screened against several transplanted tumors and the toxicity of 5-fluorouracil was characterized by delayed deaths, hematopoietic depression, diarrhea, weight loss, and hemorrhages in the lungs and intestines.
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Microestimation of citric acid; a new colorimetric reaction for pentabromoacetone.
TL;DR: Thiourea was chosen for study because of its solubility in water, ease of purification, and availability, and the development of a new colorimetric reaction with a higher extinction coefficient was of critical importance in studies.
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