Bcl-2 oncogene protects a bone marrow-derived pre-B-cell line from 5'-fluor,2'-deoxyuridine-induced apoptosis.
The bcl-2 protooncogene has been shown to protect haemopoietic precursors from programmed cell death after the removal of interleukin-3 (IL3). In the present report we show evidence that overexpression of bcl-2 in the pre-B-cell line BAF3 protects cells from apoptosis induced by treatment with the thymydilate synthase inhibitor 5'-fluor,2'-deoxyuridine (FDUR) in the presence of IL-3. Dose-response experiments analyzing the dependence of cell death on drug concentration indicated a marked resistance of BAF3bcl-2 to FDUR treatment. Cleavage of DNA into oligonucleosome-length fragments, a characteristic of apoptosis, was observed in BAF3 cells and inhibited in the cells overexpressing bcl-2. We have determined variations in the dATP and dTTP pools after FDUR treatment. Interestingly, no differences were found between both cells in the kinetics of changes in dNTP pools. Therefore, the protective effect of the Bcl-2 protein on apoptosis induced by dNTP unbalance must be ascribed to a step downstream of perturbations in the synthesis of DNA precursors and before activation of endonucleolytic cleavage of chromatin.
Oliver
F J
FJ
Instituto de Parasitología López Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
Marvel
J
J
Collins
M K
MK
López-Rivas
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005467:Floxuridine / Q000633:toxicity*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D013942:Thymine Nucleotides / Q000378:metabolism; D014162:Transfection
D003838:Deoxyadenine Nucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013942:Thymine Nucleotides; D005467:Floxuridine; D011505:Protein-Tyrosine Kinases; C026600:2'-deoxyadenosine triphosphate; C024157:thymidine 5'-triphosphate