Oghiso Y, Yamada Y, Iida H, Inaba J
Division of Radiotoxicology and Protection, National Institute of Radiological Sciences, Chiba, Japan.
J Radiat Res. 1998 Mar;39(1):61-72. doi: 10.1269/jrr.39.61.
Dose responses were compared among primary lung tumors and their histological types induced by a single inhalation exposure of female Wistar strain rats to submicron-size and polydispersed aerosols of plutonium dioxide (239PuO2). While the primary lung tumors were found only in 2.3% of the unexposed control animals, the frequency of all the primary lung tumors in the exposed animals was 44% at the mean lung dose of 0.71 Gy, and increased sharply at the doses of 1.5 Gy or more, reaching the maximum of 97% at 5.4 Gy, and the dose responses around at 1.0 Gy were different between benign and malignant lung tumors. Almost all the pulmonary tumors in the exposed animals were classified into epithelial types such as adenomas, adenocarcinomas, adenosquamous carcinomas, and squamous cell carcinomas. The dose responses were different between these tumor types as shown by the peak incidence of adenomas at 0.71 Gy, adenocarcinomas at 2.9 Gy, adenosquamous and squamous cell carcinomas at 5.4-8.5 Gy, respectively. As the magnitudes of neoplastic lesions in pulmonary carcinomas were expressed by histological scores, metaplasias and adenomatous lesions most frequently appeared at doses of 1.5 Gy, while the appearance and increase of carcinomatous lesions differed in the dose ranges as shown by the peak incidence of adenocarcinomatous lesions at 2.9 Gy, and adenosquamous or squamous lesions at 5.4-6.6 Gy. These results indicate a differential dose response of pulmonary carcinogenesis in which metaplasias and benign adenomas were induced at lower doses (< 1.0 Gy), whereas malignant carcinomas were induced at relatively higher doses (> 1.5 Gy). Together with the increase of carcinomatous lesions at higher doses, the intranuclear p53 protein accumulation was detectable, but only in a few percentages of malignant carcinomas.
将雌性Wistar品系大鼠单次吸入亚微米级多分散二氧化钚（239PuO2）气溶胶后诱发的原发性肺肿瘤及其组织学类型的剂量反应进行了比较。未暴露的对照动物中仅2.3%发现原发性肺肿瘤，暴露动物中所有原发性肺肿瘤的频率在平均肺剂量为0.71 Gy时为44%，在1.5 Gy及以上剂量时急剧增加，在5.4 Gy时达到最大值97%，1.0 Gy左右时良性和恶性肺肿瘤的剂量反应不同。暴露动物中几乎所有肺部肿瘤都归类为上皮类型，如腺瘤、腺癌、腺鳞癌和鳞状细胞癌。这些肿瘤类型之间的剂量反应不同，腺瘤的峰值发生率在0.71 Gy，腺癌在2.9 Gy，腺鳞癌和鳞状细胞癌分别在5.4 - 8.5 Gy。由于肺癌中肿瘤性病变的程度用组织学评分表示，化生和腺瘤性病变最常出现在1.5 Gy剂量时，而癌性病变的出现和增加在剂量范围内有所不同，腺癌性病变的峰值发生率在2.9 Gy，腺鳞或鳞状病变在5.4 - 6.6 Gy。这些结果表明肺致癌作用存在不同的剂量反应，其中在较低剂量（<1.0 Gy）时诱发化生和良性腺瘤，而在相对较高剂量（>1.5 Gy）时诱发恶性癌。随着较高剂量时癌性病变的增加，可检测到核内p53蛋白积累，但仅在少数百分比的恶性癌中。
