The histogenesis of hamster respiratory tumors induced by N-nitrosomethyl- n-heptylamine (NMHA) was studied by immunoelectron microscopic techniques. Dysplastic Clara cells were observed migrating from terminal bronchioles into the alveolar parenchyma by pseudopod formation, and tumors may develop from these migrating cells. Tumor cells may be well differentiated and composed of ciliated and secretory cells expressing the hamster Clara cell antigen, as shown by immunoelectron microscopy. Immunoelectron microscopic characterization of cytoplasmic structures of tumor cells will be of great help in establishing a correct histogenetic classification of lung tumors. Comparative light and electron microscopic studies suggest that the cell of origin of lung tumors may possibly determine tumor growth pattern: papillary growth indicating alveolar type II cell origin and tubulo/acinar structures formed by bronchiolar cells. Squamous metaplasia (formation of tonofilaments) was seen to evolve directly from secretory cells or from cells that fail to develop secretory features. Experimental 4-ipomeanol (IPO) treatment of hamsters with lung tumors showed that well-differentiated bronchioloalveolar and glandular portions of adenosquamous carcinomas were most susceptible to cytotoxic effects. Undifferentiated and squamous neoplasms were not responsive. No cytotoxicity was noted in mouse solid and papillary neoplasms exhibiting features of alveolar type II cells. It was further discovered in hamsters that IPO also causes severe hemorrhagic necrosis of the adrenal cortex and, at higher doses, necrosis of the olfactory epithelium. Adenocarcinomas of the nasal cavity were also susceptible to cytotoxic effects of IPO. A mouse model was developed to test tissue response of breast implant materials in the vicinity of the mammary gland. Disks of polyurethane foam were found to produce a persisting chronic granulomatous inflammatory response that included degradation and phagocytosis of polyurethane particles. Following degradation of smaller foam segments, larger particles were found to migrate into the adjacent tissue, again eliciting an inflammatory response (see also project Z01CP05353).
