© 1991 Oxford University Press
research-article |
Preneoplastic changes of xenotransplanted human distal airway epithelium induced by systemic administration of 4-nitroquinoline-1-oxide to host nude mice
Departments of Pathology, Yokohama City University School of Medicine 3-9 Fukuura Kanazawa-ku, Yokohama
1Departments of Pathology, The University of Tsukuba School of Medicine 1-1-1 Tennodai, Tsukuba
2Division of Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Disease Center 6-16-1 Tomiokahigashi, Kanazawa-ku, Yokohama, Japan
To elucidate a possible role of hematogeneously transported carcinogens in pathogenesis of peripheral lung carcinoma in humans, we investigated whether the bronchiolar and alveolar epithelial cells of adult human lung xenografts in nude mice could be a target for the chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) after its systemic administration to the host mice. Peripheral lung tissues from adult humans were transplanted s.c. into nude mice, and 4NQO (15 mg/kg) was administered s.c. to the host mice at a site distant from the xenografts at 2 and 3 weeks after transplantation. The human lung xenografts were maintained for from 20 to 52 weeks, and then serial sections were examined histologically and immunohistochemically. Three types of epithelial changes, i.e. epidermoid metaplasia, papillary hyperplasia of columnar and epidermoid cells, and atypical adenomatous hyperplasia, were induced in the 4NQO group, with a statistically significant difference for these combined epithelial lesions (P < 0.01) and for epidermoid metaplasia (P < 0.05) compared to the control group. Some epidermoid metaplasias showed significant nuclear atypia. In addition, almost all foci of epidermoid metaplasia and papillary hyperplasia contained cells positive for carcinoembryonic antigen, suggesting both types of the lesions were preneoplastic. The morphologic characteristics of the atypical adenomatous hyperplasia were very closely similar to those of the hitherto reported preneoplastic or putative neoplastic lesions in the human peripheral lung. Our results indicated that the alveolar and bronchiolar epithelial cells of human lung xenografts were affected by systemically applied 4NQO, and subsequently underwent transformation to a preneoplastic state.