Bronchogenic and alveologenic tumors in mice induced by N-nitrosopiperidine.
The aim of this study was to explore the histogenesis and carcinogenesis of pulmonary cancer induced by N-nitrosopiperidine (NPIP) in mice. NPIP is a form of N-nitrosamine found in tobacco smoke, which has been shown to be a genotoxic chemical as well as a mutagenic compound for inducing chromosome aberrations and severe clastogenicity. In this study, 80 BALB/C strain mice were injected with 0.2 mmol/kg NPIP intraperitoneally for 8 weeks, and experiments were conducted for a further 16 weeks. For the control group, 40 mice were injected with an equal volume of 0.9% NaCl. Pulmonary tissues and tumors in the NPIP-treated group were examined by light microscopy and transmission electron microscopy and compared with the control group at 4-week intervals. The mRNA levels of p53 (mutant), bcl-2, c-myc, ras, and subunits of telomerase - telomerase reverse transcriptase (TERT) and an RNA component, TR - were assayed by mPCR or RT-PCR. Twenty-two mice in the experimental group were found to develop pulmonary tumors, but none in the control group. All tumors found in the experimental group originated from alveolar type II epithelial cells. In addition, 6 of the 22 mice also developed tumors of bronchogenic origin. The expression of p53, bcl-2, c-myc, ras, and the subunits of telomerase were found to increase in all pulmonary tissues and tumors formed thereafter upon NPIP treatment. In summary, NPIP-induced mouse lung tumors exhibited morphological changes during carcinogenesis, which may be the consequence of overexpression of some genes associated with the development of carcinoma and changes in subunits of telomerase. This mouse model of lung tumor formation may be a useful tool to delineate the histogenesis and carcinogenesis of human pulmonary cancer.
Xie
Xiao-Yuan
XY
Department of Tumor Medicine, The First Affiliated Hospital, Shantou University Medical College, Shantou, P.R. China. starsea65@163.com
Shen
Jian
J
Xu
Li-Yan
LY
Li
En-Min
EM
Shen
Zhong-Ying
ZY
D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D002283:Carcinoma, Bronchogenic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009602:Nitrosamines; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D019098:Telomerase / Q000235:genetics / Q000378:metabolism
D009602:Nitrosamines; C002743:N-nitrosopiperidine; D019098:Telomerase; C509187:Tert protein, mouse