Effects of caffeine-induced defective DNA replication on SCE and chromosome aberrations produced by alkylating agents |
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Authors: | Y Shiraishi A A Sandberg |
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Institution: | 1. Laboratory of Human Cytogenetics, Department of Anatomy, Kochi Medical School, Nankoku-City, Kochi 781-51, Japan;2. Roswell Park Memorial Institute, Buffalo, NY 14263, U.S.A. |
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Abstract: | The effect of caffeine (CAF) pretreatment (during the first cell cycle) on the frequency of sister-chromatid exchanges (SCE) and chromosome aberrations induced by bifunctional(MC)- and monofunctional(M-MC)-mitomycin C, 4-nitroquinoline N-oxide (4NQO) and ethyl methanesulphonate (EMS) were examined by using a BrdU—Hoechst staining technique. When CAF was added to the cultures during the first cell cycle in the presence of BrdU and then the cultures treated with MC, M-MC, 4NQO or EMS during the second cell cycle, the effect of the CAF was synergistic, i.e., the SCE level achieved was much higher than that expected from a simple additive effect of the agents and CAF. These results do not support the concept that the process of SCE is a manifestation of CAF-sensitive post-replication repair of DNA damage (single-strand exchanges), but, instead, point to exchanges between the double-strands of the DNA duplex present in each chromatid. CAF at certain concentrations is known to significantly slow down the rate of DNA-chain growth, but not appreciably induce strand breaks. Inasmuch as CAF alone induced only a small increase in SCE rates, possible mechanisms which may induce SCE are not only related to the slowing down of the rate of DNA-chain growth, but may also involve breaks in the template strand permitting double-strand exchanges to occur. The mechanisms responsible for chemically induced SCE are also discussed. |
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Keywords: | CAF caffeine EMS ethyl methanesulfonate MC bifunctional mitomycin C M-MC momofunctional mitomycin C 4NQO SCE sister-chromatid exchange |
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