GERMLINE MUTATIONS AT EXPANDED SIMPLE TANDEM REPEAT DNA LOCI IN SENTINEL MICE

Abstract

<p>Exposure to environmental contaminants that can cause genetic damage may pose a risk of induced heritable mutations in wildlife and humans. Herring guns (Larus argentatus) nesting near integrated steel mills on the Great Lakes were shown to have elevated heritable mutation rates, but the importance of airborne and aquatic routes of contaminant exposure could not be determined. I showed that sentinel mice exposed to urban-industrial air pollution in situ near two integrated steel mills and a major highway had germ line mutation rates at expanded-simple-tandem-repeat (ESTR) DNA loci that were 1.5- to 2.0-times as high as mice exposed at a cleaner rural site. In addition, high-efficiency articulate-air filtration (HEPA) reduced mutation induction at the urban-industrial site, implicating a causal role for airborne particulate matter. These experiments identify an important role for air pollution exposure in the induction of heritable DNA mutations. I developed and tested a novel diet medium for feeding high percentages of fish to mice for toxicology experiments. This diet was then used in a study of germline mutations in mice fed fish collected from a polluted industrial site, compared to those fed fish from Atlantic Canada, or control chow. There was a non-significant trend for mice that consumed fish from the polluted site to have higher germhne ESTR mutation rates than those in the other groups. For my experiments I used out-bred Swiss-Webster mice that had not been characterized previously in studies of germline ESTR mutations. I exposed male mice to ionizing radiation to determine whether germline mutation rates increased in a dose-dependent manner following exposure to a known mutagen. Mutation rates did not increase linearly with radiation dose, showing evidence of saturation, but the estimate of doubling-dose was similar to that previously published for some inbred mouse lines.</p>