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

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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.