Rhoads K, Mahaffey J A, Sanders C L
Health Phys. 1982 May;42(5):645-56. doi: 10.1097/00004032-198205000-00007.
The distribution of inhaled 239PuO2 in rat and hamster lung was investigated up to one year postexposure in order to determine whether differences in pulmonary dose distribution could account for the apparent difference between the two species in lung tumor response. In previous life-span studies, rats developed up to 70% lung tumors at cumulative doses less than 2000 rads, whereas hamsters developed tumors in about 3% of animals at comparable or higher doses. Morphometric methods were used to quantitate the particle distribution in different lung regions of both species following exposure at levels that produced tumors in rats. The PuO2 particles were counted on autoradiograms of lung cross-sections and classified as to their location in either subpleural or internal parenchyma, lung vasculature, or major airways. Rat lung showed a greater long-term association of particles with the major airways than hamster lung. The particles also showed a greater tendency to occur in groups for rats, the difference being more pronounced in the subpleural region than in the remainder of the lung. In previous experiments, both bronchioles and subpleural fibrotic scars appeared to be the sites of origin for lung tumors. Different dose distributions within these regions may therefore affect the tumor response to inhaled 239PuO2.
为了确定肺部剂量分布的差异是否能够解释两种物种在肺部肿瘤反应上的明显差异,我们对大鼠和仓鼠在吸入239PuO2后长达一年的肺部分布情况进行了研究。在先前的寿命研究中,大鼠在累积剂量小于2000拉德时肺部肿瘤发生率高达70%,而仓鼠在同等剂量或更高剂量下肿瘤发生率约为3%。采用形态计量学方法对两种物种在能使大鼠产生肿瘤的暴露水平下不同肺区域的颗粒分布进行定量分析。在肺横截面的放射自显影片上对PuO2颗粒进行计数,并根据其位于胸膜下或内部实质、肺血管或主要气道的位置进行分类。与仓鼠肺相比,大鼠肺中颗粒与主要气道的长期关联更强。颗粒在大鼠中也更倾向于成群出现,这种差异在胸膜下区域比在肺的其余部分更为明显。在先前的实验中,细支气管和胸膜下纤维化瘢痕似乎都是肺部肿瘤的起源部位。因此,这些区域内不同的剂量分布可能会影响对吸入239PuO2的肿瘤反应。