Biochemical mechanisms of deoxycoformycin toxicity in chronic leukemias.
The in-vitro effects of deoxycoformycin (dCF) on dATP, NAD, ATP and DNA strand breaks have been evaluated in the cells from 42 patients with various types of chronic lymphoid leukemia. These included 18 with B-cell chronic lymphoid leukemias of different types (BCL); 10 with hairy cell leukemia (HCL) and 14 with T-cell chronic lymphoid leukemias of different types (TCL). The dATP concentrations in HCL, BCL and TCL increased from means of 2.9, 1.8 and 3.0 to 100.3, 68.2 and 51.3 pmol/10(6) cells respectively after 2 h with 10(-5) M dCF and 10(-4)M deoxyadenosine. After 18-24 h, the NAD levels and total double-stranded DNA decreased to 37 and 12.5% (HCL) to 36 and 21.6% (BCL) and 40 and 20.5% (TCL) of control values respectively. Similar decreases were observed in ATP levels. The results do not suggest that these measurements in vitro would predict which patients with these disorders will respond to dCF therapy. Although HCL responds particularly well to dCF in vivo, no difference in the in-vitro effects of dCF studied here could be detected between cases of HCL and the other types of chronic leukemia.
D000255:Adenosine Triphosphate / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004249:DNA Damage; D003838:Deoxyadenine Nucleotides / Q000032:analysis; D003839:Deoxyadenosines / Q000494:pharmacology; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D009243:NAD / Q000032:analysis; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D012263:Ribonucleosides; D009243:NAD; D003070:Coformycin; D015649:Pentostatin; D000255:Adenosine Triphosphate; C026600:2'-deoxyadenosine triphosphate