Project at a Glance

Title: Role of nitrogen dioxide and ozone in cancer metastsis and systemic adverse effects

Principal Investigator / Author(s): Richters, Arnis

Contractor: USC School of Medicine

Contract Number: A4-064-33

Research Program Area: Health & Exposure

Topic Areas: Health Effects of Air Pollution


In recent years, we have utilized a unique biological probe (living cancer cells) to detect NO2 and 03 induced adverse effects. The indicator for adverse effects has been the increased incidence of melanoma nodule development in the lungs from the intravenously injected cancer cells. Our past studies have demonstrated that inhalation of 0.3 - 0.8 ppm of N02. Will facilitate melanoma cell metastasis to the lungs of exposed animals, but exposure to ozone (0.15 ppm) does not exhibit this phenomenon. In experiments carried out under this contract we have demonstrated that exposure to a combination of NO2 and O3 at 0.35 ppm and 0.15 ppm, respectively results in facilitation of blood-borne melanoma cell metastasis. It appears that in this system NO2 may be the more harmful component. Of the many possible cellular systems that NO2 may affect, the defense system and the lung blood capillaries would be the most likely targets, and damage to these cells could account for these findings. Our immunological studies of the defense system have indicated the following: 1) spleen T lymphocytes, T-helper and T-supressor cells showed a trend towards lower percentages of these cells after 12,weeks of NO2 exposure and 2) the functional test for Natural Killer (NK) cells indicated suppressed cytotoxicity following 6 weeks of exposure. The lung capillary lining cells of exposed animals showed a greater degree of cell injury as revealed by ultrastructural studies and increased number of thrombi in lung capillaries. Alterations in these two systems would also imply systemic NO2 effect with a number of possible adverse consequences. Even though these studies were carried out in an animal model, 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 a subclinical disease process. The knowledge of pollutant effects on different cells of the defense system could provide a sensitive indicator for adverse effects and should p1ay a role in setting air quality standards.

For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753

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