Cytogenetic, Cytotoxic, and Cell-Cycle Effects of 3-Aminobenzamide in Human Lymphoblastoid Cells Proficient or Deficient in Nucleotide Biosynthesis

Abstract

In some recent studies it has been reported that 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) polymerase [7, 10] also inhibits the pathway for de novo synthesis of DNA precursors. Specifically, 3AB inhibits the metabolism of glucose and methionine into precursors of DNA in WI-L2 lymphoid cells [6], C3H mouse fibroblasts [1], and Chinese hamster ovary (CHO) cells [4]. It has been suggested that some of the reported effects of 3AB, such as its effect on cell-cycle progression [8], may be due to a disturbance in nucleotide precursor pathways rather than an inhibition of poly(ADP-ribose) synthesis [1–4, 6]. To test this hypothesis, we have examined the effects of 3AB on SCE induction, cytotoxicity, and cell-cycle progression in three different human lymphoblastoid cell lines; two deficient in salvage nucleotide synthesis pathways and one competent in both salvage and de novo nucleotide synthesis. We hypothesized that if 3AB inhibits de novo nucleotide synthesis pathways, then cells deficient in salvage nucleotide synthesis pathways should be more sensitive to the various effects of 3AB, especially its cytotoxic and cell-cycle effects.