Effects of actinomycin D on mouse thymus in vivo chromatin degradation to nucleosomes and inhibition of RNA and protein synthesis.
The administration of actinomycin D in toxic doses (4 mg/kg i.p.) to mice induces a progressive degradation of thymus chromatin. The course of this damage is slower than the radiation-induced chromatin degradation; it starts at 6-8h and culminates at 24 h after actinomycin D injection, when already most of the treated mice are dying. The inhibition of the [2-14C] orotic acid incorporation into rapidly labelled RNA by actinomycin D is substantially less expressed in the thymus than in the liver. The course of chromatin degradation correlates with the onset of the inhibition of protein synthesis in the thymuses of actinomycin D-treated mice. This demonstrates that, starting from the 6th h after actinomycin D administration, irreversible changes appear in the thymocytes that lead to chromatin degradation and cellular death. Contrary to the action of cycloheximide, the treatment with actinomycin D aggravates the chromatin degradation induced by irradiation. A comparative electrophoretic analysis of the DNA fragments (in native state and denatured) isolated from thymus chromatin of mice treated with actinomycin D (and/or irradiated) demonstrated that the chromatin DNA is degraded only in the internucleosomal segments yielding DNA fragments of nucleosomal size. Similarly to the effect of other agents leading to chromatin damage in vivo, the actinomycin D-induced degradation does not affect the DNA in the nucleosomal segments of chromatin.
N V
NV
Ermolaeva
J
J
Matyásová
M
M
Skalka
D000818:Animals; D002843:Chromatin / Q000187:drug effects* / Q000528:radiation effects; D004247:DNA / Q000032:analysis; D003609:Dactinomycin / Q000008:administration & dosage / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D009707:Nucleosomes / Q000032:analysis / Q000187:drug effects* / Q000528:radiation effects; D012313:RNA / Q000378:metabolism* / Q000528:radiation effects; D012269:Ribosomal Proteins / Q000378:metabolism / Q000528:radiation effects; D013950:Thymus Gland / Q000187:drug effects* / Q000528:radiation effects; D013997:Time Factors
D002843:Chromatin; D009707:Nucleosomes; D012269:Ribosomal Proteins; D003609:Dactinomycin; D012313:RNA; D004247:DNA