Induction and inhibition of friend erythroleukemia cell differentiation by pyrimidine analogs: Analysis of the requirement for intracellular accumulation and incorporation into DNA
Alkyldeoxyuridines which differ from thymidine by a C5 substitution of straight or branched alkyl chains of two to six carbon atoms have been tested for their ability to be taken up, phosphorylated, and incorporated into DNA. Analysis of the uptake of 5-ethyl-2'-deoxyuridine and 5-propyl-2'-deoxyuridine (n-PrdU) - similar to both thymidine and 5-bromo-2'-deoxyuridine - indicates that transport is dependent upon a functional cellular thymidine kinase. All of the aforementioned pyrimidines with the exception of n-PrdU are phosphorylated to the triphosphate and incorporated into DNa. The homologs 5-iso-propyl-2'-deoxyuridine (iso-PrdU) and 5-hexyl-2'-deoxyuridine are neither transported into the cell, phosphorylated, nor incorporated into DNA. These analogs were tested (i) for their ability to induce in the absence of dimethyl sulfoxide and (ii) to determine whether they enhance or inhibit dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells. Inhibition of erythroid differentiation appears to require the incorporation of thymidine analogs into DNA, and thus only 5-ethyl-2'-deoxyuridine and 5-bromo-2'-deoxyuridine were effective in inhibiting dimethyl sulfoxide-induced differentiation. The observation that iso-PrdU, and to a lesser extent n-PrdU and 5-propyldeoxyuridine monophosphate, induce differentiation under conditions in which they are not detectable intracellularly is strong evidence that this class of inducer acts at the cell membrane.
- Research Organization:
- Abteilung Molekularbiologie, Universitat Hamburg, Hamburg 13
- OSTI ID:
- 5891872
- Journal Information:
- Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 2:8; ISSN MCEBD
- Country of Publication:
- United States
- Language:
- English
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550800 -- Morphology
59 BASIC BIOLOGICAL SCIENCES
ALKYL RADICALS
ANTIMETABOLITES
AZINES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
BROMOURACILS
BUDR
CELL CONSTITUENTS
CELL DIFFERENTIATION
CELL MEMBRANES
CONTROL
DEOXYURIDINE
DISEASES
DRUGS
ENZYME INDUCTION
ENZYME INHIBITORS
ENZYMES
FUNCTIONS
GENE REGULATION
GENES
GENETIC CONTROL
GENETIC ENGINEERING
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LEUKEMIA
MATERIALS
MEMBRANES
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEST CONTROL
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PYRIMIDINES
RADICALS
RIBOSIDES
THYMIDINE
TOXICITY
TRANSFERASES
URACILS