DNA repair induction by cytostatic drugs in proliferating and quiescent MRC-5 cells.
The repair of DNA damage is closely related to cell cycle, in terms of both modulation of repairing ability throughout the cell cycle and perturbations in replication. We have studied the induction of Unscheduled DNA Synthesis (UDS) in human fibroblasts (MRC-5) by some chemotherapeutic agents, selected for their different mechanisms of action. To take into account the interaction between repair and replication systems, the experiments were performed in both proliferating and quiescent cultures; semiconservative DNA synthesis inhibition was examined by microphotometric measurements in the same autoradiographic preparations used for UDS analysis. Vincristine, methotrexate and 6-thioguanine induced no UDS. Adriamycin, actinomycin D, and, to a lesser extent, cyclophosphamide and thiotepa gave positive results only in proliferating cultures, whereas bleomycin was an effective inducer of UDS in quiescent cells, with weak UDS levels in proliferating ones. In all these cases, the combined analysis of UDS and semiconservative DNA synthesis inhibition proved to be of value in the assessment of interaction between drugs and DNA in proliferating cultures. The results of our experiments emphasize the importance of the cycling conditions in the cellular response to DNA damage.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects*; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D013866:Thioguanine / Q000494:pharmacology
D000970:Antineoplastic Agents; D001761:Bleomycin; D003609:Dactinomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D004247:DNA; D013866:Thioguanine; D008727:Methotrexate