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 inhibitorof the enzyme ADP-ribosyltransferase (ADPRT). This hypersensitivityis not found with the non-inhibitory analogue, 3-aminobenzoate.The NAD content of 46BR cells is similar to that of fibroblastsfrom normal human donors, as is the decrease in NAD contentfollowing treatment with dimethylsulphate. Both the activityof ADP-ribosyltransferase and its inhibition by 3AB in permeabiliz-edcells are similar in 46BR and in normal cell strains. High concentrationsof 3AB interfere with purine metabolism in cultured cells. Againthis effect is similar in 46BR and normal cells. Thus thereis no apparent anomaly either in the activity of ADPRT or inthe gross effects of 3AB in 46BR. The sensitivity to 3AB maybe caused by a defect in a specific acceptor for the ADP-ribosesynthesized by ADPRT, or in some as yet undiscovered actionof the inhibitor.