J Biomed Opt. 2011 Jul;16(7):070503. doi: 10.1117/1.3597723.
Intrigued by our recent finding that the nuclear refractive index is significantly increased in malignant cells and histologically normal cells in clinical histology specimens derived from cancer patients, we sought to identify potential biological mechanisms underlying the observed phenomena. The cell cycle is an ordered series of events that describes the intervals of cell growth, DNA replication, and mitosis that precede cell division. Since abnormal cell cycles and increased proliferation are characteristic of many human cancer cells, we hypothesized that the observed increase in nuclear refractive index could be related to an abundance or accumulation of cells derived from cancer patients at a specific point or phase(s) of the cell cycle. Here we show that changes in nuclear refractive index of fixed cells are seen as synchronized populations of cells that proceed through the cell cycle, and that increased nuclear refractive index is strongly correlated with increased DNA content. We therefore propose that an abundance of cells undergoing DNA replication and mitosis may explain the increase in nuclear refractive index observed in both malignant and histologically normal cells from cancer patients. Our findings suggest that nuclear refractive index may be a novel physical parameter for early cancer detection and risk stratification.
受我们最近的发现的启发，即核折射率在癌症患者临床组织学标本中的恶性细胞和组织学正常细胞中显著增加，我们试图确定观察到的现象背后的潜在生物学机制。细胞周期是一个有序的事件系列，描述了细胞生长、DNA 复制和有丝分裂的间隔，这些事件发生在细胞分裂之前。由于异常的细胞周期和增殖增加是许多人类癌细胞的特征，我们假设观察到的核折射率增加可能与来自癌症患者的细胞在细胞周期的特定点或阶段（多个）的丰度或积累有关。在这里，我们表明，在经历细胞周期的同步细胞群体中可以看到固定细胞的核折射率的变化，并且核折射率的增加与 DNA 含量的增加强烈相关。因此，我们提出，正在进行 DNA 复制和有丝分裂的细胞的丰度可能解释了癌症患者的恶性和组织学正常细胞中观察到的核折射率增加。我们的研究结果表明，核折射率可能是早期癌症检测和风险分层的新物理参数。
