Nuclear chromatin condensation of mouse lymphoma (L-1210) cells by methylnitrosourea. An electron microscopic and biochemical study.
When the mouse lymphoma (L-1210) cells are treated with methylnitrosourea (MNU) at 37 degrees C for 30 min and then cultured for 4 h in a normal medium nuclear structure and functions of the cells are changed. We have investigated the mechanism as to how nuclear structure and functions are changed by MNU. In MNU-treated cells euchromatin area diminishes and chromatin condensation occurs. [3H]thymidine and [3H]uridine uptakes of the MNU-treated cells decrease. In contrast, when the MNU-treated cells are cultured in the presence of 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) synthetase changes of nuclear structure do not appear. [3H]Thymidine and [3H]uridine uptakes are partially and almost completely recovered, respectively. Autoradiographs of the cells labelled with [3H]NAD, a substrate of poly(ADP-ribose) synthetase show that silver grains due to [3H]ADP-ribose are densely located only in the cells where chromatin condensation occurs. Chromatin-bound proteins of molecular masses 20-25 X 10(3) daltons are specifically poly(ADP-ribosyl)ated in the MNU-treated cells. These results suggest that MNU-induced chromatin condensation is caused by poly(ADP-ribosyl)ation of chromatinbound proteins.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology*; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D008854:Microscopy, Electron; D009607:Nitrosourea Compounds / Q000494:pharmacology*
D002843:Chromatin; D009607:Nitrosourea Compounds; D008770:Methylnitrosourea