Biochemical basis for the enhanced toxicity of deoxyribonucleosides toward malignant human T cell lines.
Human malignant T cell lines have high levels of deoxyribonucleoside phosphorylating activity and low levels of deoxyribonucleotide dephosphorylating activity. When incubated with deoxyadenosine or thymidine, the malignant T cell lines rapidly accumulate toxic concentrations of dATP and dTTP, respectively. This unusual pattern of deoxyribonucleotide metabolism renders the malignant T cells especially vulnerable to the toxic effects of deoxyribonucleosides and related analogues.
D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism; D003853:Deoxyribonucleosides / Q000633:toxicity*; D003854:Deoxyribonucleotides / Q000378:metabolism; D006801:Humans; D009708:Nucleotidases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D003854:Deoxyribonucleotides; D009708:Nucleotidases