-transparent.png){kind=logo}
We compared deoxyadenosine (AdR)- and cyclic AMP (cAMP)-induced cell cycle arrest and cytotoxicity in wild type and mutant S49 cells to determine whether they resulted from the same or different mechanisms. Cyclic AMP and deoxyadenosine are synergistic rather than additive in cytotoxicity assays, suggesting different mechanisms of toxicity. Although cyclic AMP causes cell death after 72 h, in concentrations sufficient to result in cell cycle arrest it is reversible with virtually no cytotoxicity for at least 24 h, whereas AdR-induced cell cycle arrest is lethal and irreversible. AdR-induced G1 cell cycle arrest results in diminished ribonucleotide reductase activity but the kinetics of this inhibition differ from cyclic AMP-induced cell cycle arrest. Cyclic AMP arrest and cytotoxicity depend on cyclic AMP-dependent protein kinase (PKA) activity, whereas AdR toxicity does not differ between cell lines with or without PKA activity. Furthermore, deoxycytidine prevents AdR cell cycle arrest and cytotoxicity but has no effect on cyclic AMP G1 arrest. Finally, comparison of cytofluorographic patterns of G1-arrested cells suggests that the AdR block is later in G1 than cyclic AMP-induced cell cycle arrest. In summary, these data show that while the mechanisms of cell cycle arrest and cytotoxicity of cyclic AMP and deoxyadenosine are uncertain, they do appear to involve different pathways.
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
June 1980,
Proceedings of the National Academy of Sciences of the United States of America,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
May 2024,
Experimental parasitology,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
August 2012,
Clinical oral investigations,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
January 2005,
Birth defects research. Part A, Clinical and molecular teratology,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
October 1972,
Nature: New biology,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
July 2008,
Cancer biology & therapy,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
May 1985,
Molecular and cellular biochemistry,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
November 1980,
Biochimica et biophysica acta,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
March 1975,
Proceedings of the National Academy of Sciences of the United States of America,
D A Albert, and
E Nodzenski, and
G H Cruz, and
J Kuchibholtla, and
J Kowalski
May 1986,
Cancer research,
