DNA repair replication, DNA breaks and sister-chromatid exchange in human cells treated with adriamycin in vitro.
The effects of adriamycin (AM) on DNA repair replication, the frequency of sister-chromatid exchange (SCE), the rate of cell proliferation and the frequency of DNA strand breaks were studied in human cells in vitro. No repair replication was observed in lymphocytes exposed to AM in concentrations up to 10(-3) moles/l. DNA repair replication induced by UV and alkylating agents was not affected by a concentration of AM that completely inhibited cell proliferation (10(-6) moles/l). Fibroblasts exposed to AM at 10(-4) moles/l in the presence of hydroxyurea showed an increase of strand breaks and cross-links in DNA. When AM was added to UV-irradiated fibroblasts, there was an increase of DNA strand breaks in addition to the breaks caused by UV alone. Similar effects were observed in lymphocytes. A dose-dependent increase of SCE was observed in lymphocytes exposed to low concentrations of AM (less than 10(-7) moles/l). At higher concentrations the increase of SCE levelled off, and cell proliferation became severely inhibited. There was no evidence of removal of SCE-inducing damage in cells exposed to AM during G0 or G1. The level of SCE induced in the third cell cycle after treatment with AM was not different from that induced during the first two cell cycles. These results suggest that the various genotoxic and cytotoxic effects of AM are caused by different types of cellular damage. Moreover, AM-induced DNA damage persists for several cell cycles in human cells in vitro and seems to be resistant to repair activity.
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000235:genetics; D004317:Doxorubicin / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008466:Mechlorethamine / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012867:Skin / Q000187:drug effects*; D012879:Skin Physiological Phenomena; D014466:Ultraviolet Rays
D004277:DNA, Single-Stranded; D008466:Mechlorethamine; D004317:Doxorubicin; D008741:Methyl Methanesulfonate