Model systems for investigating the cancer risk from environmental uranium: Lymphoma cell lines and yeast cells take up uranium from culture media Free

B87

The long-term objective of the project is to understand the cancer risk posed by environmental uranium species. The purpose of the present study was to test model systems for investigating the biological consequences of uranium interactions with mammalian cells. The project is relevant to concerns within the Navajo Nation that environmental contamination from uranium mining in the 1940s to 1970s has led to cancer disparities. Cancer risks from environmental uranium (i.e., through chronic exposure to contaminated water and airborne soil) would likely be due to the chemistry of the uranium species, rather than to radioactivity. The reason is that the long half-life of the radioactive uranium isotopes, 10⁵ - 10⁹ years, limits the amount of radiation damage that could result from their decay as well as the low exposure concentrations. Increased oxidative stress has previously been proposed as a chemical mechanism of cellular damage and potential genotoxicity following exposure to uranium. In this study, we cultured lymphoma-derived murine cell lines in media containing 0 to 600 μM uranyl acetate or uranyl nitrate. Cell lines with increased resistance to oxidative stress were compared to sensitive cells. Growth rates were measured based on the number of viable cells over time. Uptake of uranium into the cells was assessed by inductively coupled plasma mass spectrophotometry measurements of total uranium content in acid-digested cell extracts. Given the genetic tools available for yeast studies, this organism could be valuable for elucidating molecular mechanisms of uranium genotoxicity. Uranium uptake into DNA was investigated by growing yeast cultures in media containing 0 to 600 μM uranyl acetate or uranyl nitrate, extracting and acid-digesting the DNA and using inductively coupled plasma mass spectrophotometry to measure total uranium content. These analyses showed that the lymphoma cell lines took up uranium from the media in a concentration-dependent manner. The highest uranium concentrations were found in the oxidative stress resistant cell line. This cell line, however, also had the fastest growth rate. The uranium content found in the DNA extracted from the yeast cells was proportional to the concentration of uranium present in the growth media. We conclude that the lymphoma cell lines and yeast accumulate uranium from their environment and will be useful models for determining mechanisms by which exposure to environmental uranium increases the risk of mammalian cells acquiring cancer-promoting genetic changes. Future questions to be addressed are whether resistance to oxidative stress allows cells to accumulate higher levels of uranium or whether uranium uptake is simply dependent on growth rate, the chemical nature of the interaction of uranium with DNA and whether this interaction leads to DNA mutations.