Niacin prevents DNA strand breakage by adenosine deaminase inhibitors.
The adenosine deaminase inhibitors deoxycoformycin and erythro-9-(2-hydroxy-3 nonyl) adenine (EHNA) induce single-strand DNA breaks in cultured human lymphocytes. Deoxycoformycin produced a significant number of strand breaks (4-fold increase compared to controls) and EHNA induced strand breaks in a dose-dependent manner. Strand breaks stimulate repair by poly(ADP-ribosylation) which requires NAD+ as a cofactor. Niacin is a precursor of NAD+ and when preincubated with human lymphocytes prior to exposure to adenosine deaminase inhibitors, strand breakage was reduced significantly. The administration of niacin may represent an approach to decreasing the toxicity associated with these agents.
Weitberg
A B
AB
Division of Hematology/Oncology, Roger Williams General Hospital, Providence, Rhode Island 02908.
Corvese
D
D
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D009525:Niacin / Q000494:pharmacology*; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin / Q000494:pharmacology*
D058892:Adenosine Deaminase Inhibitors; D009525:Niacin; D015649:Pentostatin; C010192:9-(2-hydroxy-3-nonyl)adenine; D004247:DNA; D009700:Nucleoside Deaminases; D000225:Adenine