Possible participation of Ca2+, Mg2+-dependent endonuclease in liver DNA fragmentation after N-methyl-N-nitrosourea treatment.
We examined the fragmentation of DNA treated with N-methyl-N-nitrosourea under conditions in which Ca2+, Mg2+-dependent endonuclease is active. The molecular mass of DNA found in mouse liver slices treated with methylnitrosurea in the presence of Ca2+ plus Mg2+ was 4 X 10(5) Da. Similar results were obtained with a reconstituted system containing partially purified Ca2+, Mg2+-dependent endonuclease and methylnitrosurea-treated DNA. The enzyme extensively cleaved methylnitrosurea-treated DNA, compared with non-treated DNA. The methylnitrosurea-treated nuclear proteins obtained from mouse liver nuclei had no effect on the DNA fragmentation by the enzyme. Using closed-circular DNA treated with methylnitrosurea, the enzyme produced single-strand cuts in the DNA, as was seen in non-treated, closed-circular DNA, however, the rate of hydrolysis was increased. Ca2+, Mg2+-dependent endonuclease thus warrants further investigation, with regard to the precise mechanism of extensive degradation of DNA in cells treated with carcinogenic alkylating agents.
D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D004247:DNA; D004260:DNA Repair; D004279:DNA, Viral; D004533:Egtazic Acid / Q000494:pharmacology; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver; D008770:Methylnitrosourea; D051379:Mice; D008970:Molecular Weight; D009607:Nitrosourea Compounds; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D051381:Rats
D004279:DNA, Viral; D009607:Nitrosourea Compounds; D011064:Poly Adenosine Diphosphate Ribose; D004533:Egtazic Acid; D008770:Methylnitrosourea; D004247:DNA; D004706:Endodeoxyribonucleases; C029367:calcium magnesium dependent endodeoxyribonuclease