Is Ap4A involved in DNA repair processes?
Hepatoma tissue culture (HTC) cells were incubated in the presence of the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to study the variations in the bisnucleosides polyphosphates (Ap4X) pool size. A transient but sensitive accumulation of these compounds is observed; if 3-aminobenzamide (3AB) which is a potent inhibitor of the ADP-ribosyltransferase (ADPRT) is added after the MNNG treatment, a more pronounced and persistent accumulation of Ap4X can be seen. A moderate heat-shock (30 min at 43 degrees C) results also in a small accumulation of Ap4X but the shape of the accumulation curve is quite different and the increase of the Ap4X pool is not sensitive to the presence of 3AB. However, both MNNG treatment and hyperthermia cause a marked inhibition of protein synthesis. On the other hand, the ADPRT activity is enhanced in the presence of MNNG whereas hyperthermia has little or a slightly inhibitory effect on this activity. These results suggest that MNNG treatment triggers an Ap4X accumulation in eukaryotic cells different from that observed after heat-shock and it seems likely that these compounds are involved in the DNA excision repair system in which the ADPRT enzyme is also implicated.
Gilson
G
G
Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
Ebel
J P
JP
Remy
P
P
D000227:Adenine Nucleotides / Q000378:metabolism*; D000478:Alkylation; D001549:Benzamides / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D015226:Dinucleoside Phosphates; D006358:Hot Temperature; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D000227:Adenine Nucleotides; D001549:Benzamides; D015226:Dinucleoside Phosphates; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; C020733:diadenosine tetraphosphate; C025160:3-aminobenzamide; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases