Wax Adam, Yang Changhuei, Müller Markus G, Nines Ronald, Boone Charles W, Steele Vernon E, Stoner Gary D, Dasari Ramachandra R, Feld Michael S
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
Cancer Res. 2003 Jul 1;63(13):3556-9.
We present a quantitative study of the nuclear morphometry of epithelial cells in an animal model of esophageal carcinogenesis. Changes in the size and texture of cell nuclei as a result of neoplastic transformation and chemopreventive action are observed in situ using a new optical technique, angle-resolved low-coherence interferometry (a/LCI). The capabilities of a/LCI are demonstrated via quantitative in situ measurements of the nuclear morphometry of basal epithelial cells, approximately 50-100 microm beneath the tissue surface without the need for exogenous contrast agents or tissue fixation. The measurements quantify changes in nuclear size, characterized by average diameter, and nuclear texture, characterized by fractal dimension of the subcellular structures. Using this technique, we observed changes in the morphometry of rat esophageal epithelial cells in response to treatment with the carcinogen N-nitrosomethylbenzylamine. In addition, morphometric changes were observed in the esophagi of rats treated with N-nitrosomethylbenzylamine and two chemopreventive agents, difluoromethylornithine and perillyl alcohol. These agents induced either apoptosis in the basal epithelium (difluoromethylornithine) or both apoptosis and vacuolation of basal epithelial cells (perillyl alcohol). Vacuolation was associated with cellular toxicity. The light-scattering measurements were compared with histological images of the same tissues. The potential of a/LCI as a noninvasive means to investigate the development of epithelial neoplasia and for tracking the efficacy of chemopreventive agents appears high. This technique also may provide a new screening tool for intraepithelial neoplasia.
我们对食管癌变动物模型中上皮细胞核形态进行了定量研究。利用一种新的光学技术——角分辨低相干干涉测量法（a/LCI），在原位观察了肿瘤转化和化学预防作用导致的细胞核大小和纹理变化。通过对组织表面以下约50 - 100微米处基底上皮细胞核形态进行定量原位测量，展示了a/LCI的能力，无需外源性造影剂或组织固定。这些测量量化了以平均直径为特征的核大小变化以及以亚细胞结构的分形维数为特征的核纹理变化。利用该技术，我们观察到用致癌物N-亚硝基甲基苄胺处理后大鼠食管上皮细胞形态的变化。此外，在用N-亚硝基甲基苄胺以及两种化学预防剂二氟甲基鸟氨酸和紫苏醇处理的大鼠食管中也观察到了形态计量学变化。这些药剂要么诱导基底上皮细胞凋亡（二氟甲基鸟氨酸），要么诱导基底上皮细胞凋亡和空泡化（紫苏醇）。空泡化与细胞毒性有关。将光散射测量结果与相同组织的组织学图像进行了比较。a/LCI作为一种非侵入性手段来研究上皮肿瘤的发展以及追踪化学预防剂疗效的潜力似乎很高。该技术还可能为上皮内瘤变提供一种新的筛查工具。
