Influence of apurinic acid on programmed synthesis in different in vitro systems.

Apurinic acid (APA) obtained by mild acid hydrolysis of DNA was degraded to low-molecular-weight fragments. The fraction with an average molecular weight of 19,500 daltons reduced cell proliferation (L5178Y mouse lymphoma cells) on a molar basis more sensitively than did APA fractions of a lower molecular weight. Reduced cell proliferation was due to cytostatis rather than cytotoxicity. Cells treated with APA showed a 28% higher volume. The DNA-dependent DNA polymerase (type 11) is noncompetitively inhibited by APA, with fragments of 19,500 daltons exerting the highest inhibitory activity (with regard to molar basis). Treated APA, in which aldehyde groups have been reduced, shows a much lower inhibitory potency and acts competitively with untreated APA. The inhibition observed is caused by APA per se and not by secondary products of low molecular weight derived from APA. The DNA polymerases isolated from Escherichia coli (type I) and from oncogenic RNA viruses are not affected by APA. The influence of modified DNA on DNA-dependent RNA polymerase from L5178Y cells is low. No effect is observed in a protein-synthesizing, cell-free system. Among the nucleases tested, only the DNase I activity is inhibited by APA; this inhibition is competitive with respect to DNA. A nuclease activity that degrades APA has been detected in APA-treated L5178Y cells. The action of this enzyme is discussed in relation to the recovery of cell proliferation in cells inhibited by APA.