Dissimilar effects of 尾-lapachone- and hydroxyurea-induced DNA replication stress in root meristem cells of Allium cepa
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- 作者：Aneta 呕abka ; Pawe艂 Trzaskoma ; Janusz Maszewski
- 关键词：尾-Lapachone ; Cell cycle checkpoints ; DNA damage ; Hydrogen peroxide ; Hydroxyurea ; 纬-H2AX histones
- 刊名：Plant Physiology and Biochemistry
- 出版年：December, 2013
- 年：2013
- 卷：73
- 期：Complete
- 页码：282-293
- 全文大小：2166 K
文摘
Two anticancer drugs, 尾-lapachone (尾-lap, a naphthoquinone) and hydroxyurea (HU, an inhibitor of ribonucleotide reductase), differently affect nuclear morphology and cell cycle control mechanisms in root meristem cells of Allium cepa. The 18聽h treatment with 100聽渭M 尾-lap results in a lowered number of M-phase cells, increased occurrence of mitotic abnormalities, including over-condensation of chromosomes, their enhanced stickiness, formation of anaphase bridges, micronucleation and reduced mitotic spindles. Following prolonged incubations using high doses of 尾-lap, cell nuclei reveal dark-red fluorescence evenly distributed in chromatin surrounding the unstained regions of nucleoli. Both drugs generate H2O2 and induce DNA double strand breaks, which is correlated with 纬-phoshorylation of H2AX histones. However, the extent of H2AX phosphorylation (including the frequency of 纬-H2AX foci and the relative number cells creating phospho-H2AX domains) is considerably reduced in root meristem cells treated jointly with the 尾-lap/HU mixture. Furthermore, various effects of caffeine (an inhibitor of ATM/ATR cell cycle checkpoint kinases) on 尾-lap- and HU-induced 纬-phoshorylation of H2AX histones and the protective activity of HU against 尾-lap suggest that their genotoxic activities are largely dissimilar. 尾-Lap treatment results in the induction of apoptosis-like programmed cell death, while HU treatment leads to cell adaptation to replication stress and promotion of abnormal nuclear divisions with biphasic interphase/mitotic states of chromatin condensation.