title: The bis(adenosin-N6-yl) alkanes, a family of potential dinucleoside polyphosphate analogue precursors. Mechanism of growth inhibition and suppression of adenosine toxicity in lymphoid cells.
abstract: The potential diadenosine polyphosphate analogue precursor, bis(adenosin-N6-yl)dodecane (A[CH2]12A) (Chen, H. & McLennan, A. G. (1993) Eur. J. Biochem. 213, 935-944.) is equally toxic to both wild-type and adenosine-kinase-deficient BHK cells at concentrations up to 100 microM; at higher concentrations, wild-type cells are more sensitive, as are cells over-expressing adenosine kinase. Thus both the nucleoside and its nucleotide products are toxic. In contrast to adenosine toxicity, the toxicity of A[CH2]12A to S-49 T-lymphoma cells could not be reversed by uridine or by L-homocysteine thiolactone. A[CH2]12A and all its shorter chain bis(adenosin-N6-yl)alkane homologues could relieve the toxicity of low adenosine concentrations (< 20 microM) to S-49 cells, mainly through inhibition of adenosine kinase, while relief of the toxicity of high adenosine concentrations (> 20 microM) required the longer chain homologues. A[CH2]12A at 10 microM completely eliminated adenosine toxicity. Deoxyadenosine toxicity could also be relieved, but only that due to low concentrations (< 4 microM). A[CH2]12A had only a slight stimulatory effect on S-adenosylhomocysteine-hydrolase activity.
authors.affiliation: Department of Biochemistry, University of Liverpool, England.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: A G
authors.initials: AG
authors.lastname: McLennan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D043383:Adenosylhomocysteinase; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003839:Deoxyadenosines / Q000633:toxicity; D004347:Drug Interactions; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006867:Hydrolases / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000494:pharmacology
chemical_list: D003839:Deoxyadenosines; D006710:Homocysteine; C070819:bis(N(6)-adenosyl)dodecane; C007957:homocysteine thiolactone; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine; D014529:Uridine