Snyder C A, Solomon J J
New York University Medical Center, Nelson Institute of Environmental Medicine, Tuxedo 10987.
Cancer Lett. 1993 Aug 31;72(3):157-61. doi: 10.1016/0304-3835(93)90122-p.
In order to investigate some of the mechanisms underlying the carcinogenicity of inhaled propylene oxide (PO), the deposition and persistence of inhaled tritiated PO in the DNA of the nasal cavities, tracheae and lungs of rats were investigated. The results of dose/response exposure protocols revealed clear gradients for binding throughout the respiratory mucosa; the highest levels of binding were in the nasal mucosa and the lowest were in the lungs. Gradients became steeper as exposure concentrations were lowered. The persistence studies revealed that bound tritium declined in nasal mucosal DNA with apparent bi-exponential kinetics while clearance from the tracheal and pulmonary DNA was much slower and occurred with apparent mono-exponential kinetics. Consequently, although the initial levels of binding of inhaled PO are lower in the trachea and lungs than in the nasal cavity, the slow clearance of PO from the DNA in these organs could increase the chances of a mutational event.
为了研究吸入环氧丙烷（PO）致癌性的一些潜在机制，对吸入的氚标记PO在大鼠鼻腔、气管和肺部DNA中的沉积和持久性进行了研究。剂量/反应暴露方案的结果显示，在整个呼吸道黏膜中，结合存在明显的梯度；结合水平最高的是鼻黏膜，最低的是肺。随着暴露浓度降低，梯度变得更陡。持久性研究表明，结合的氚在鼻黏膜DNA中以明显的双指数动力学下降，而从气管和肺DNA中的清除则慢得多，且以明显的单指数动力学发生。因此，尽管吸入的PO在气管和肺中的初始结合水平低于鼻腔，但PO从这些器官的DNA中缓慢清除可能会增加发生突变事件的几率。
