Scheduled and unscheduled DNA synthesis in chick embryo liver following X-irradiation and treatment with DNA repair inhibitors in vivo.
Three hours following X-irradiation of chick embryos with doses of 4 and 8 Gy the in vitro incorporation of tritiated thymidine [( 3H]dT) into DNA (scheduled DNA synthesis, ss) of hepatocytes was reduced to about one-third. Within 24 h after the exposure, ss returned to control values. The return of ss to a normal rate could be strongly inhibited by 2',3'-dideoxythymidine (ddT), and to a lesser extent by 1-beta-D-arabinofuranosylcytosine (araC). In strong contrast to ss, the hydroxyurea (hu)-resistant [3H]dT incorporation (unscheduled DNA synthesis, us) showed a highly significant increase 24 h after treatment of the embryos with araC and/or X-irradiation. Autoradiographic studies revealed no change of total [3H]dT labelling frequency in the whole chick embryo liver 24 h after treatment with araC and/or X-irradiation, but a persistent depression of ss and a simultaneous increase of us. The histological discrimination between affected and non-affected areas argue for a stimulation of DNA synthesis as an antecedent of subsequent mitosis and reparative proliferation adjacent to cell necrosis. It is suggested that the fast recovery of ss in the 12-15-day-old chick embryo is due to an efficient DNA repair system for which DNA polymerase beta is important. The increase of hu-resistance may be an expression of an aberrant DNA synthesis.
Stammberger
I
I
Institut für Pharmakologie, Toxikologie und Pharmazie, Tierärztlichen Fakultät der Universität München, F.R.G.
Schmahl
W
W
Tempel
K
K
D000818:Animals; D001345:Autoradiography; D002642:Chick Embryo; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects*; D015224:Dideoxynucleosides / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D018119:Stavudine; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D015224:Dideoxynucleosides; D003561:Cytarabine; D014316:Tritium; D004247:DNA; D018119:Stavudine; D013936:Thymidine