An experimental model was designed where the frequency of blood-borne cancer cell metastases to the lungs of animals was used as an indicator to detect adverse effects of inhaled nitrogen dioxide (NO2). Animals were exposed to air containing 0.40 +/- 0.05 ppm or 0.80 +/- 0.05 ppm of NO2. After the appropriate exposure periods, the animals were infused intravenously with B16 mouse melanoma cells. At 3 wk post-infusion the animals were killed and the lungs were examined for melanoma nodule development. The lungs of the NO2-exposed animals contained a significantly higher number of melanoma nodules than the lungs of control animals (P less than .0025). These results indicate that inhalation of ambient or near ambient levels of NO2 influences the metastasis of blood-borne cancer cells. This raises the possibility that similar events may occur in the human population.

Periderm granules in the support cells of regenerating feathers of mature male Jungle Fowls were studied ultrastructurally and histochemically. Histochemical results showed the absence of carbohydrate and lipid, and the presence of protein in the periderm granules. The periderm granules were measured at successive levels of feather regeneration. The mean size of the periderm granules increased significantly as the regenerating feather matured, and this observation was suggestive of a storage function, perhaps of surplus of waste protein. The cells in which the periderm granules are found also contain glycogen. There are numerous desmosomal junctions on their interdigitating plasma membranes. These transient cells may collect waste, provide nutrition, and serve as a protective barrier for the definitive cells of the regenerating feather.

Studies have been carried out to determine whether the inhalation of ambient levels of nitrogen dioxide (NO2), a common air pollutant, could influence the frequency of bloodborne cancer cell metastasis to the lungs. B16 mouse melanoma cells were used as an in vivo test model. The results have indicated that animals inhaling ambient levels of NO2 developed a significantly higher number of melanoma nodules in their lungs than the animals inhaling ifitered air. Thus, a new concept for the action of air pollutants is proposed. The question is raised whether similar events are taking place in urban human populations.The presence of pollutants in the environment, especially those with carcinogenic properties, has been of great concern to environmental health scientists. In view of this, many studies have been directed toward the identification of cancer-causing agents in the environment (1-4). However, the problem of cancer involves not only the development and presence ofneoplastic cells at a primary site, but also the ability of these cells to migrate, seed, and proliferate in distant organs and tissues. The importance of cancer cell dissemination and metastasis has been emphasized by many investigators and has been stated particularly well by Day, who wrote that, "even though the cause of cancer is important, in the clinical case it is the spread-the phenomenon of metastasisthat is of much more immediate concern in the human situation" (5). Moreover, considering that a significant segment of the population is already affected by cancer together with the probability that one in four individuals will develop cancer (6), the question arises as to the role environmental pollutants play not only in the causation of cancer or carcinogenesis, but in the progression of the disease, particularly the dissemination of cancer cells and development of metastases.The development and progression of cancer is a very complex process (Fig. 1). It is possible that different air pollutants could act at different sites

The effects of ambient levels of NO2 on the spleens of adult and newborn Swiss Webster (S/W) mice were determined. Spleens were evaluated by the following criteria: (1) spleen weight, expressed as a percent of the body weight (% spleen weight), (2) size of the spleen lymphoid nodules as determined by computed image analysis, (3) spleen cell counts, and (4) histopathologic evaluation. Data for NO2-exposed animals were compared with data for control animals that inhaled filtered air. Totals of 217 control and 217 NO2-exposed animals were studied. After 6 wk of exposure to NO2 at ambient levels (0.35 +/- 0.05 ppm), the following significant changes were observed in the spleens of exposed mice: (1) increase in % spleen weight (p less than 0.0025), (2) increase in size of spleen lymphoid nodules (p less than 0.01), (3) smaller increase in spleen cell number per given weight increment of spleen as determined by correlation coefficients (p less than 0.0125) and linear regression analysis of spleen cell counts, and (4) an apparently greater predominance of red cells in the red pulp. It is concluded that inhalation of NO2 is associated with quantifiable spleen changes, which may prove to be useful indicators for assessing effects of inhaled NO2.