Project at a Glance
Title: Role of air pollutants in facilitation of cancer cell metastasis
Principal Investigator / Author(s): Richters, A.
Contract Number: a2-128-33
Research Program Area: Health & Exposure
Topic Areas: Health Effects of Air Pollution, Vulnerable Populations
In recent years we have established an animal model (mouse) in which we have utilized a biological probe circulating cancer cells to detect adverse effects following NO2 inhalation. The indicator for the adverse NO2 effects has been the increased incidence of lung metastases in the exposed animals. With respect to the latter, our studies have indicated that inhalation of NO2 facilitates blood borne cancer cell metastasis to the lungs of exposed animals. This is a new aspect of NO2 inhalation hazards which has not been recognized before our studies. The studies described in this report were designed to improve the sensitivity of this method and to employ it to evaluate other air pollutant effects. The experiments were also carried out to determine the effects of NO2 on the growth of a primary rat carcinoma. With respect to the latter, adenocarcinoma cells were transplanted into the mammary fat pads of the exposed and control rats and this transplant was considered to be a "primary" cancer. In all of the experiments there were two groups of animals; one was exposed to an ambient concentration of a particular air pollutant and the other received clean filtered air. The animals were exposed in special environmental chambers, with continuous monitoring of the NO2 or 03 concentrations. Following the appropriate exposure periods, all of the mice were injected intravenously with cancer cells (biological probe). The functioning of mouse splenic natural killer cells was also evaluated following NO2 exposure. After three weeks the lungs were examined for the presence of melanoma nodules or metastases. The results have indicated that by utilizing a lower number of cells in the biological probe, the sensitivity of the method could be improved. We have been able to demonstrate that the mice exposed to 0.4 & 0.05 ppm of NO2 developed not only significantly more metastases in their lungs than the controls, but that there were significantly more mice with metastases in the exposed group. The NO2 apparently also enhanced the growth of the transplanted cancer cells in those animals which were more sensitive to the NO2 insult. The animals exposed to 0.15 & 0.02 ppm of O3 also developed more metastases in their lungs than the controls, but the difference was not statistically significant and the meaning of the this finding was not clear. The results also revealed significantly lower body weights in O3 exposed animals which indicated that even at this low level the animals were affected adversely by 03. The experiment with spleen cells suggested that the exposed and the control animal spleen cells responded differently to the cancer cells, reflecting some ozone affect on the spleen cells. In general, these experiments have provided new information which indicates that inhalation of common air pollutants at ambient levels may be more hazardous than previously recognized. Even though these studies were carried out in animal model systems, we have to suspect that the same or similar events may take place in humans residing in a polluted environment. This may be particularly true with individuals who are sensitive to air pollutants and those who have various diseases, including cancer.
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