NAD and the synthesis of (ADP-ribose)n in a human cell strain (46BR) hypersensitive to the lethal effects of 3-aminobenzamide.
The cell strain 46BR, derived from an immunodeficient individual, is hypersensitive to the lethal effects of DNA-damaging agents, and of 3-aminobenzamide (3AB), the latter being an inhibitor of the enzyme ADP-ribosyltransferase (ADPRT). This hypersensitivity is not found with the noninhibitory analogue, 3-aminobenzoate. The NAD content of 46BR cells is similar to that of fibroblasts from normal human donors, as is the decrease in NAD content following treatment with dimethylsulphate. Both the activity of ADP-ribosyltransferase and its inhibition by 3AB in permeabilized cells are similar in 46BR and in normal cell strains. High concentrations of 3AB interfere with purine metabolism in cultured cells. Again this effect is similar in 46BR and normal cells. Thus there is no apparent anomaly either in the activity of ADPRT or in the gross effects of 3AB in 46BR. The sensitivity to 3AB may be caused by a defect in a specific acceptor for the ADP-ribose synthesized by ADPRT, or in some as yet undiscovered action of the inhibitor.
Poirier
V
V
James
M R
MR
Arlett
C F
CF
Lehmann
A R
AR
D000246:Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D001549:Benzamides / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000473:pathology; D066298:In Vitro Techniques; D009243:NAD / Q000032:analysis*; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D009713:Nucleotidyltransferases / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D000246:Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases