一定浓度的甲醛可以引起蛋白质的异常修饰、功能丧失、细胞死亡。虽然甲醛的细胞毒性已见报道,但甲醛影响神经细胞周期及其分子机制等尚不明确.本文采用不同浓度甲醛与神经母细胞瘤细胞系SH-SY5Y共孵育,观察到甲醛对细胞周期的影响取决于甲醛的浓度.当甲醛浓度([FA])≤0.1 mmol/L(细胞培养48 h),细胞周期与对照相比,无显著性差异.当甲醛浓度增加(0.1 mmol/L〈[FA]≤0.2 mmol/L),S期和G2/M期细胞比例显著增加;当[FA]=0.3 mmol/L时,细胞增殖被显著抑制,大量细胞滞留在S期(46.28%),G2/M期细胞仅占16.05%.将细胞同步到G2/M期,用0.1~0.3 mmol/L甲醛孵育,尽管G2/M期细胞都有一定程度的减少,但S期细胞显著增加;将细胞同步化到S期,与0.1 mmol/L甲醛孵育,则G2/M期细胞有一定程度的减少;与0.3 mmol/L甲醛孵育,表现为G2/M细胞显著减少,S期细胞极度增加.在相同条件下,Sprague-Dawley(SD)大鼠原代皮层神经元,也表现出G2/M期细胞比例随甲醛浓度升高而降低,S期细胞比例随之增加的现象.当0.1 mmol/L≤[FA]≤0.2 mmol/L时,细胞出现明显的早期或晚期凋亡;当[FA]≥0.3 mmol/L时,DNA损伤明显,细胞出现凋亡和部分坏死.以上结果提示,低浓度甲醛(0.1 mmol/L≤[FA]≤0.2 mmol/L)主要通过引起DNA超甲基化而抑制S期DNA的合成,高浓度甲醛([FA]≥0.3 mmol/L)则造成DNA的损伤,从而影响细胞周期的进程.
A certain concentration of formaldehyde can cause protein misfolding, cell death and biological dysfunction. Though it has been reported that formaldehyde has cytotoxicity, how formaldehyde affects cell cycle of neural cells and the molecular mechanism still needs to be clarified. In this study, neuroblastoma cell line SH-SY5Y was utilized to incubate with formaldehyde and the effect of formaldehyde on cell cycle was in formaldehyde concentration-dependent manner. No significant changes in cell cycle could be detected when [FA] ≤0.1 mmol/L (cells were incubated for 48 h), while the percentages of cells in S phase and G2/M phase were markedly increased with the elevation of formaldehyde concentration (0.1 mmol/L 〈 [FA] ≤0.2 mmol/L). In the medium with 0.3 mmol/L formaldehyde, 46.28% of cells were in S phase while only 16.05% of them were in G2/M phase, that is, cell proliferation was obviously inhibited under the conditions. When cells were synchronized at G2/M phase, formaldehyde (0.1 -0.3 mmol/L) could markedly increase the number of cells in S phase, though, to some extent, the number of ceils in G2/M phase decreased. When cells were synchronized at S phase, 0.1 mmol/L formaldehyde could decrease the number of cells in G2/M phase, while 0.3 mmol/L formaldehyde could markedly decrease the number of cells in G2/M phase and significantly increase that in S phase. In the presence of formaldehyde, primary neurons of SD rat exhibited similar changes in cell cycle as that in SH-SY5Y cells. Furthermore, early and late apoptosis was markedly observed when 0.1 mmol/L ≤[FA] ≤0.2 mmol/L, while DNA were obviously damaged and most cells were apoptosis and some of them underwent necrosis when [FA] ≥ 0.3 mmol/L. In sum, formaldehyde at a low concentration (0.1 mmol/L ≤ [FA]≤ 0.2 mmol/L) mainly suppresses DNA synthesis in S phase via hypermethylation of global DNA, while formaldehyde at a higher concentration ([FA] ≥ 0.3 mmol/L) causes DNA damage, both of them lead to the aberrant effects o