SCE evaluations in human lymphocytes after G0 exposure to mitomycin C. Lack of expression of MMC-induced SCEs in cells that have undergone greater than two in vitro divisions.
We conducted a series of experiments designed to determine whether DNA damage induced in G0 lymphocytes by mitomycin C (MMC) would be expressed as sister-chromatid exchanges during the second and third post-treatment cell cycles. Lymphocytes from normal donors were exposed to MMC for 2 h prior to culture in the presence of phytohemagglutinin. MMC-treated and control cells were subsequently exposed to bromodeoxyuridine (BrdUrd) for the entire culture period (i.e. 48 h or 72 h) or for the terminal 24 h of 72-h cultures. We observed a 3-4-fold increase in SCEs in MII metaphases from lymphocytes treated with MMC and cultured in the presence of BrdUrd for the entire culture period. In contrast, in replicate cultures of MMC-treated lymphocytes that were exposed to BrdUrd for the terminal 24 h only, the SCE frequency in uniformly harlequinized metaphases was not significantly different from that observed in control cultures. We interpret these data as providing evidence that MMC-induced lesions (or alterations) in the DNA of G0 lymphocytes are probably expressed as SCEs during the first period of mitogen-induced DNA synthesis, and that these lesions do not persist and give rise to SCEs in subsequent cell divisions.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D006801:Humans; D007399:Interphase / Q000187:drug effects*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin