Effect of Particulate Matter on DNA Deletions in Mice

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DESCRIPTION (provided by applicant): Mexico City is home to more than 18 million individuals who breathe the most polluted air in North America. Particulate Matter (PM) contained in air pollution consists of a staggering number of known carcinogens and there is some epidemiological indication that exposure to PM causes cancer in people. We have shown in preliminary results that an exposure to diesel exhaust particles significantly increases the frequency of DNA deletions in mice. Genetic instability, in particular DNA deletions are involved in the etiology of cancer. In addition, many other carcinogens induce such deletions, several of them through an oxidative mechanism. Aim 1 is to determine whether PM from different parts of Mexico City increase the frequency of DNA deletions in mice. The findings could shed mechanistic light on the potential association between PM exposure and cancer, which is currently unknown. Since oxidative stress seems to be involved in the adverse biological activity of PM and our deletion assay is very sensitive towards prooxidants, aim 2 is to determine whether antioxidant exposure may reduce the potential effect of PM on the frequency of deletions. The results obtained in this project could reinforce the notion that PM act through generation of oxidative stress and potentially, after similar studies have been carried out in humans, could lead to the recommendation of taking nutritional antioxidants by occupationally PM exposed workers. This research will be done primarily in Mexico at Universidad Nacional Autonoma de Mexico and the Institute Nacional de Cancerologia in collaboration with Alvaro R. Osornio Vargas and Claudia Garcia Cuellar as an extension of NIH grant #R01 ES09519.