Biomaterial Database

Derangement of DNA synthesis in erythroleukaemia. Normal deoxyuridine suppression and impaired thymidine incorporation in bone marrow culture. 1980

K C Das, and G Garewal, and D Mohanty

Deoxyuridine (dU) suppression test (i.e. ability of exogenous dU to suppress the incorporation of subsequently added 3H-thymidine into DNA) and the incorporation of 3H-thymidine (3H-TdR) alone without dU were studied in bone marrow cultures from 10 patients with erythroleukaemia, 10 patients with vitamin B12/folate-deficient megaloblastic anaemia and 10 haematologically normal subjects. Despite morphological resemblance between megaloblastosis in erythroleukaemia and nutritional megaloblastosis, the dU suppression values in erythroleukaemia were within normal range in contrast to abnormal dU suppression in vitamin B12/folate-deficient megaloblastic bone marrows. The incorporation of 3H-thymidine alone was significantly lower in erythroleukaemia than in normal or vitamin B12/folate-deficient megaloblastic bone marrows. Autoradiographic studies showed that 3H-TdR labelling indices as well as mean grain count (MGC) of basophilic and polychromatic erythroblasts were significantly lower in erythroleukaemia than in normal or vitamin B12/folate-deficient bone marrows. The reduced incorporation of 3H-TdR in erythroleukaemia erythroblasts was probably not due to deficiency of the salvage pathway enzyme, thymidine kinase, since MTX (10(-5) M) which blocks the de novo pathway of thymine-DNA synthesis, enhanced the incorporation of 3H-TdR into erythroblasts in erythroleukaemia as well as in normal bone marrows. A high intracellular pool of thymidine-triphosphate (dTTP) due to defective DNA synthesis may allosterically inhibit thymidine kinase and 3H-TdR incorporation.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D001853	Bone Marrow	The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.	Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003857	Deoxyuridine	2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.	(beta 1-(2-Deoxyribopyranosyl))thymidine
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004915	Leukemia, Erythroblastic, Acute	A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.	Di Guglielmo's Disease,Erythremic Myelosis,Erythroblastic Leukemia, Acute,Erythroleukemia,Leukemia, Myeloid, Acute, M6,Myeloid Leukemia, Acute, M6,Di Guglielmo Disease,Acute Erythroblastic Leukemia,Acute Erythroblastic Leukemias,Di Guglielmos Disease,Disease, Di Guglielmo,Disease, Di Guglielmo's,Erythremic Myeloses,Erythroblastic Leukemias, Acute,Erythroleukemias,Leukemia, Acute Erythroblastic,Leukemias, Acute Erythroblastic,Myeloses, Erythremic,Myelosis, Erythremic
D005260	Female		Females
D005494	Folic Acid Deficiency	A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)	Deficiency, Folic Acid,Acid Deficiencies, Folic,Acid Deficiency, Folic,Deficiencies, Folic Acid,Folic Acid Deficiencies