Abstract
A class of arabinosyladenine-resistant baby hamster kidney (BHK) cell mutants, isolated in our laboratory, shows cross-resistance to deoxyadenosine, alteration of adenosine kinase, elevation of spontaneous mutation rate, and extreme sensitivity to adenosine. One of these adenosine sensitive mutants, ara-slOd, was isolated spontaneously and studies with Ador revertants suggest the involvement of a single pleiotropic mutation. The enhanced adenosine toxicity in ara-slOd cells can be attributed to pyrimidine nucleotide starvation and to at least one other mechanism, which is associated with a 200-fold elevation of IMP, 3–5 fold elevation of ATP, GTP, S-adeno- sylmethionine (AdoMet) and methylthioadenosine (MeSAdo).
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V. L. Chan and P. Juranka, Isolation and preliminary characterization of 9-β-D-arainofuranosyladenine-resistant mutants of baby hamster cells, Somat. Cell Genet., 7: 147 – 160 (1981).
V. L. Chan, S. Guttman, and P. Juranka, Mutator genes of baby hamster kidney cells, Mol. Cell Biol., 1: 568 - 571 (1981).
V. L. Chan, F. Meffe, S. Guttman, P. Juranka, and S. M. Archer, in: “Manipulation and Expression of Genes in Eucaryotes” (P. Nagley, A. W. Linnane, W. J. Peacock, and J. A. Pateman, eds.), pp. 55 – 58, Acad. Press, Sydney (1983)
M. Ehrlich and R. H. Wang, 5-methylcytosine in eukaryotic DNA, Science, 212: 1350 – 1357 (1981).
A. J. Fero, in: “Transmethylation” (E. Usdin, R. T. Borchardt, and C. R. Crevelling, eds.), pp. 117 – 126, Elsevier North Holland, Inc., New York (1979)
I. H. Fox and W. N. Kelley, The role of adenosine and 2’-deoxy- adenosine in mammalian cells, Ann. Rev. Biochem., 47: 655 – 686 (1978).
E. R. Giblett, J. E. Anderson, F. Cohen, B. Pollara, H. J. Meuwissen, Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity, Lancet, 2: 1067 – 1069 (1972).
L. J. Gudas, A. Cohen, B. Ullman, and D. W. Martin, Jr., Analysis of adenosine-mediated pyrimidine starvation using cultured wild-type and mutant mouse T lymphoma cells, Somat. Cell. Genet., 4: 201 – 219 (1978).
J. F. Henderson, Effects of nucleoside analoges on purine metabolism, Pharmacol. Ther., 2: 751 – 769 (1978).
K. Ishii and H. Green, Lethality of adenosine for culturedmammalian cells by interference with pyrimidine biosynthesis, J. Cell Sci., 13: 429 – 439 (1973).
J. M. Johnston and N. M. Kredich, Inhibition on methylation by adenosine in adenosine deaminase inhibited, phytohemagglutinin-stimulated human lymphocytes, J. Immunol., 123: 97 – 103 (1979).
N. M. Kredich and M. S. Hershfield, Pertubation in S-adenosyl- homocysteine and S-adenosylmethionine metabolism: effects on transmethylation, Adv. Enzy. Regul., 18: 181 – 191 (1980).
N. M. Kredich and D. W. Martin, Jr., Role of S-adenosylhomo- cysteine in adenosine-mediated toxicity in cultured mouse T lymphoma cells, Cell, 12: 931 – 938 (1977).
R. E. Law and L. Miller, Effect of 5’-methylthioadenosine on nuclear morphology and RNA metabolism in cultured Xenopus laeviscells, Exp. Cell Res., 135: 435 – 438 (1981).
R. E. Law, R. M. Sinibaldi, M. R. Cummings, and A. J. Ferro, Inhibition of RNA synthesis in salivary glands of Drosophila melanogaster by 5’-methy1thioadenosine, Biochem. Biophys. Res. Commun., 73: 600 – 606 (1976).
O. H. Lowry, N. F. Rosenburg, A. L. Farr, and R. J. Randall, Protein measurement with folin phenol reagent, J. Biol. Chem., 193: 265 – 275 (1951).
T. McDonald, H. G. Sachs, C. W. Orr, and J. D. Ebert, External potassium and baby hamster kidney cells: intracellular ions, ATP, growth, DNA synthesis and membrane potential, Develop. Biol., 28: 290 – 303 (1972).
A. E. Pegg, R. T. Borchardt, and J. K. Coward, Effects of inhibitors of spermidine and spermine synthesis on polyamine con centrations on growth of transformed mouse fibroblasts, Biochem. J., 194: 79 – 89 (1981).
F. D. Ragione and A. E. Pegg, Effect of analogues of 5’-methyl thioadenosine on cellular metabolism, Biochem. J., 210: 429 – 435 (1983).
A. Raina, K. Tuomi, and R. L. Pajula, Inhibition of the synthesis of polyamines and macromolecules by 5’-methylthioadeno- sine and 5’-alkylthiotubercidine in BHK 21 cells, Biochem. J. 204: 697 – 703 (1982).
A. Razin and A. D. Riggs, DNA methylation and gene function, Science, 210: 604 – 610 (1980).
C. P. Stanners, G. I. Eliceri, and H. Green, Two types of ribosomes in mouse-hamster hybrid cells, Nature New Biol., 230: 52 – 54 (1971).
A. A. Vandenbark, A. J. Ferro, and G. L. Barney, Inhibition of lymphocyte transformation by a naturally occurring metabolite 5’-methylthioadenosine, Cell. Immunol., 49: 26 – 33 (1980).
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© 1985 Plenum Press, New York
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Chan, VL., Ho, H.J. (1985). Multiple Mechanisms of Adenosine Toxicity in an Adenosine Sensitive Mutant of Baby Hamster Kidney (BHK) Cells. In: de Serres, F.J. (eds) Genetic Consequences of Nucleotide Pool Imbalance. Basic Life Sciences, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2449-2_6
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DOI: https://doi.org/10.1007/978-1-4613-2449-2_6
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