Faculty Bibliography

Human papillomavirus type 16 is highly associated with cervical carcinoma. Here we report families of transgenic mice produced by the microinjection of a dimer repeat sequence of the human papillomavirus type 16 genome. Thirty-two transgenic animals in four families developed multiple organ malignancies that appeared in middle age without other intervention. The tumor phenotype of poorly differentiated carcinomas or malignant lymphomas and the transgene cosegregate in these lineages. The tumors arise in the subcutaneous compartment, thoracic cavity, or abdomen; are widely metastatic; and grow rapidly in nude mice. No cervical lesions were identified in six females examined. No rearrangements in transgene E6/E7, E2, and E1 regions were found in tumor tissues, and the truncated E2 region, which was thought to play an important role in human cervical carcinogenesis, was not needed for tumorigenesis in these animals. The transgenic mice produce RNA from the E6/E7 open reading frames, which has been identified in both the carcinomas and the lymphomas, but RNA from the E2 open reading frame is present only in malignant T-cell lymphomas and not in carcinomas, hyperplastic lymphoid tissue, or normal lymphoid tissue.

In the present study we investigated the in vitro effects of the tumor promoter phorbol myristate acetate (PMA) on the accessory function of mouse spleen dendritic cells (DC) in mitogenesis. The effects of the PMA, a protein kinase C (PKC) activator, depended on dose. If pretreated with < 50 ng/ml of PMA for 3 h, DC activity was enhanced by about two-fold; whereas > or = 200 ng/ml of PMA decreased DC activity with an inhibition rate about 50% (in early response DC activity showed a moderate increase). Our results indicate that the function of DC, a potent accessory population, can be further enhanced by a low dose of PMA. This is circumstantial evidence that DC activity can be up-regulatal via PKC activation. That a high dose of PMA inhibits DC activity might be a mechanism by which PMA promotes carcinogenesis.

This is a report of the study on the immunological status of alveolar macrophages (aM phi) in patients with lung cancer (LC, n = 27) and benign pulmonary diseases (BD, n = 26). Patients were undergone bronchoalveolar lavage by fiberoptic bronchoscopy. aM phi in the lavage fluid isolated by adherence on plastic surface were examined in vitro for their cytostatic and cytolytic activities against tumor target cells, secretion of interleukin 1 (IL-1) and tumor necrosis factor (TNF), intracellular IL-1 activity and mRNA expression of IL-1 beta and TNF-alpha. aM phi, both non-activated and activated, were shown to be highly cytostatic against P815 cells by 3H-TdR post-labelling assay. There was no statistical difference between the LC and BD group. As shown by isotope release assay, regardless of being activated or not, aM phi were not cytolytic against P815 and NS-1 cells in both groups of patients. TNF activity could be demonstrated in the culture supernatants of aM stimulated with LPS. Statistically, the TNF activity was not different in the two groups of patients. Spontaneous release of TNF activity was occasionally detected in unstimulated aM phi. While both intracellular and extracellular IL-1 activity of unstimulated aM phi was demonstrated in the two patient groups, the former activity was 1 to 5 times as high as the latter. When stimulated with LPS, there was some increase in extracellular but not intracellular IL-1 activity. mRNA expression of IL-1 beta and TNF-alpha by dot blot hybridization was demonstrable in aM phi from both patient groups irrespective of activation. These results indicate that the immune status of aM phi in lung cancer patients examined does not differ from that in patients with benign pulmonary diseases.