| Abstract |
AA8 Chinese hamster ovary cells were treated with halogenated nucleosides analogues of thymidine, namely C1dU, 5-iodo-2\'-deoxyuridine (IdU), and 5-bromo-2\'-deoxyuridine (BrdU), following different experimental protocols. The purpose was to see whether incorporation of exogenous pyrimidine analogues into DNA could interfere with normal chromosome segregation. The endpoint chosen was endoreduplication, that arises after aberrant mitosis when daughter chromatids segregation fails. Treatment with any of the halogenated nucleosides for two consecutive cell cycles resulted in endoreduplication, with a highest yield for C1dU, intermediate for IdU, and lowest for BrdU. The frequency of endoreduplicated cells paralleled in all cases the level of analogue substitution into DNA. Our results seem to support that thymidine analogue substitution into DNA is responsible for the triggering of endoreduplication. Besides, the lack of any effect on endoreduplication when C1dU was present for only one S-period strongly suggest that it is the nature of template, and not nascent DNA, that plays a major role in chromosome segregation. Taking into account that topoisomerase 11 cleaves DNA at preferred sequences within its recognition/binding sites, the likely involvement of the enzyme is discussed. (C) 2003 Elsevier Science B.V. All rights reserved. |
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