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Histogenesis of Rat Lung Tumors induced by N-Nitrosodiethylamine (DEN)

N-亚硝基二乙胺 (DEN) 诱导的大鼠肺肿瘤的组织发生

基本信息

批准号：
06670620
负责人：
HASHIMOTO Shuichi
金额：
$ 1.28万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

1. We found the formation of lung tumors in the all rats of DEN and DEN+PIP group. The mean number of grossly visible tumor nodules in controle, DEN and DEN+PIP group was 0, 3, 4.5 in 32 week treatment rats and 0.5, 16, 7 in 48 week treatment rats, respectively. The number of DEN 48 week group was the highest, but there was no statistical significance among the number and those of other groups.2. At 32 weeks the tumorous lesions of atypical adenomatous hyperplasia, well differentiated adenocarcinoma and the admixture of both the two lesions were found in the alveolar region. The papillary proliferation of tumors at the end of the bronchiolar region and their growth to the adjacent alveolar spaces were also recognized, suggesting their bronchiolar epithelial cell origin. At 48 weeks multiple tumorous lesions consisting of adenocarcinoma with severe cellular pleomorphism and scattered mitotic figures were noticed.3. Immunohistochemically the SP-A was expressed in the tumor cells of both 32 and 48 week treatment rats. In contrast to this no apparent CC10 reactivity was recognized in all tumor cells even in the Clara like tumor cells, which suggests the depression of CC10 expression in the tumor cells.4. The mean number of PCNA Labeling Index (L.I.) (the number of positive tumor cells/1000 tumor cells) in each groups was 167.5 in DEN 32 week, 159.5 in DEN+PIP 32 week, 364 in DEN 48 week and 174 in DEN+PIP 48 week treatment group. The mean number of L.I.in DEN 48 week treatment group was statistically higher then that of any other groups, and this was well matched the tendency of tumor formation.5. The mean number of PCNA L.I.in DEN+PIP 48 week treatment group was statistically lower than thet of DEN 48 week treatment group, and from this and the tendency of lower tumor formation in DEN+PIP than that in DEN treatment group the inhibition of DEN induced tumorigenesis by PIP was suggested.

1. 我们发现DEN和DEN+PIP组大鼠均有肺肿瘤形成。对照组、DEN和DEN+PIP组32周大鼠肉眼可见肿瘤结节的平均数目分别为0、3、4.5个，48周大鼠肉眼可见肿瘤结节的平均数目分别为0.5、16、7个。DEN 48周组次数最多，但与其他组比较，差异无统计学意义。32周时，在肺泡区发现非典型腺瘤性增生、高分化腺癌和两种肿瘤的混合病变。细支气管末端肿瘤的乳头状增生及其向邻近肺泡间隙的生长也被识别，提示其起源于细支气管上皮细胞。48周时可见腺癌组成的多发肿瘤病变，伴严重的细胞多形性和分散的有丝分裂象。SP-A在治疗32周和48周的大鼠肿瘤细胞中均有表达。与此相反，在所有肿瘤细胞中，甚至在Clara样肿瘤细胞中，均未发现明显的CC10反应性，提示CC10在肿瘤细胞中的表达受到抑制。PCNA标记指数（L.I.）的平均数目各组阳性肿瘤细胞数（每1000个肿瘤细胞数）分别为：DEN 32周167.5个，DEN+PIP 32周159.5个，DEN 48周364个，DEN+PIP 48周174个。4 . DEN治疗组48周l.i数平均高于其他各组，与肿瘤形成趋势吻合较好。DEN+PIP治疗组48周的平均PCNA l.i.数明显低于DEN治疗组48周的平均PCNA l.i.数，且DEN+PIP治疗组的成瘤率明显低于DEN治疗组，提示PIP对DEN诱导的肿瘤发生有抑制作用。