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An analysis of multiple mechanisms of adenosine toxicity in baby hamster kidney cells
Author(s) -
Archer Sherry,
Juranka Peter F.,
Ho Jeok H.,
Chan VoonLoong
Publication year - 1985
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041240209
Subject(s) - adenosine kinase , adenosine , adenosine deaminase , deoxycoformycin , toxicity , adenosine deaminase inhibitor , biology , biochemistry , hamster , chemistry , pharmacology , microbiology and biotechnology , organic chemistry
Analysis of the response of baby hamster kidney cells to adenosine in the presence of the adenosine deaminase inhibitor erythro‐9‐(2‐hydroxy‐3‐nonyl) adenine has revealed two distinct mechanisms of toxicity. The first is apparent at low concentrations of adenosine (< 5 μM) and is dependent upon the presence of a functional adenosine kinase. The initial toxicity is abolished by uridine, is unrelated to the inhibition of ribonucleotide reductase, and is accompanied by a decrease in the size of the pyrimidine nucleotide pool. Toxicity at higher concentrations of adenosine is adenosine kinase independent and is potentiated by homocysteine thiolactone. An elevation in the intracellular level of S‐adenosylhomocysteine, which was observed following treatment with higher concentrations of adenosine (> 10 μM), is believed to mediate toxicity at these levels. Interestingly, BHK cells were resistant to intermediate levels of adenosine. The mechanism of resistance is currently unknown, but appears unrelated to a lack of inhibition of aenosine deaminase. It is proposed that substrate inhibition of adenosine kinase may be a determinant of this property.