Nylen E S, Becker K L, Joshi P A, Snider R H, Schuller H M
Section of Endrocrinology, Veterans Administration Medical Center, Washington, D.C. 20422.
Am J Respir Cell Mol Biol. 1990 Jan;2(1):25-31. doi: 10.1165/ajrcmb/2.1.25.
Combined exposure of hamsters to 60% hyperoxia and the carcinogen diethylnitrosamine for 6 wk resulted in the development of lung tumors. This was associated with progressive loss of body weight as well as increases in the pulmonary-associated peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT). After 3 wk of exposure, multiple bronchial epithelial hyperplastic foci were noted, along with increased lung levels of MB and iCT as well as increased serum levels of MB. At this time, immunocytochemistry revealed the presence of MB and iCT within hyperplastic pulmonary neuroendocrine (PNE) cells. In addition, the localization of MB to alveolar type II cells was noted, along with the presence of lamellar bodies and secretion granules in these cells on electron microscopy. After 6 wk of exposure, distinctive microscopic pulmonary tumorlets were seen. These tumorlets were associated with a marked increase in lung and serum MB, and to a lesser extent lung and serum iCT. At this time, MB and iCT were localized exclusively to these abnormal PNE cell sites. These results, which may have relevance in humans, suggest that endogenous peptides may be important components in the process of development of neuroendocrine cancer.
将仓鼠置于60%的高氧环境中，并使其接触致癌物二乙基亚硝胺6周，结果导致肺部肿瘤的发生。这与体重的逐渐减轻以及肺相关肽、哺乳动物蛙皮素（MB）和免疫反应性降钙素（iCT）的增加有关。暴露3周后，观察到多个支气管上皮增生灶，同时肺中MB和iCT水平升高，血清中MB水平也升高。此时，免疫细胞化学显示增生的肺神经内分泌（PNE）细胞内存在MB和iCT。此外，还注意到MB定位于Ⅱ型肺泡细胞，电子显微镜观察发现这些细胞内存在板层小体和分泌颗粒。暴露6周后，可见明显的微观肺微小瘤。这些微小瘤与肺和血清中MB的显著增加以及肺和血清中iCT的轻度增加有关。此时，MB和iCT仅定位于这些异常的PNE细胞部位。这些结果可能与人类情况相关，提示内源性肽可能是神经内分泌癌发生过程中的重要组成部分。
