The relationship between the disassembly of microtubules during G1 and the enhancement of DNA synthesis by colchicine in mouse fibroblasts stimulated with peptide growth hormones.
By immunofluorescent staining to visualize the cytoplasmic microtubular cytoskeleton in mouse fibroblasts we have ascertained that after a relatively short exposure of cells to colchicine, microtubules remain disassembled for a prolonged period of time after cells are transferred to a colchicine-free medium. In contrast to the persisting effects of colchicine, a brief exposure of cells to nocodazole first induces the expected disruption of microtubules followed by regeneration of the cytoskeleton within a few hours after removal of extracellular drug. These results shed light on our previous finding that quiescent mouse fibroblasts first treated with colchicine and then transferred to colchicine-free medium exhibit an enhanced proliferative response to EGF and insulin, whereas cells treated in a similar manner with nocodazole show no enhancement of DNA synthesis stimulated by peptide growth hormones. We conclude that cytoplasmic microtubules must remain disaggregated during the prereplicative G1 period in order for cells to exhibit the enhancing effects of the microtubule-disrupting drugs on DNA synthesis.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001921:Brain / Q000502:physiology; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004285:Dogs; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007328:Insulin / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015739:Nocodazole; D051381:Rats; D013552:Swine; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D007328:Insulin; D014404:Tubulin; D004815:Epidermal Growth Factor; D015739:Nocodazole; D003078:Colchicine