Hundreds of thousands of people worldwide live or work in close proximity to steel mills. Integrated steel production generates chemical pollution containing compounds that can induce genetic damage (1, 2). Previous investigations of herring gulls in the Great Lakes demonstrated elevated DNA mutation rates near steel mills (3, 4) but could not determine the importance of airborne or aquatic routes of contaminant exposure, or eliminate possible confounding factors such as nutritional status and disease burden. To address these issues experimentally, we exposed laboratory mice in situ to ambient air in a polluted industrial area near steel mills. Heritable mutation frequency at tandem-repeat DNA loci in mice exposed 1 km downwind from two integrated steel mills was 1.5-to 2.0-fold elevated compared with those at a reference site 30 km away. This statistically significant elevation was due primarily to an increase in mutations inherited through the paternal germline. Our results indicate that human and wildlife populations in proximity to integrated steel mills may be at risk of developing germline mutations more frequently because of the inhalation of airborne chemical mutagens.
Integrated steel mills produce chemical mutagens that contaminate atmospheric and aquatic environments (1, 2), and may pose a genetic hazard to humans and wildlife. Herring gulls (Larus argentatus) nesting near steel mills on the Great Lakes were shown to have higher germline mutation rates at minisatellite DNA loci than those at rural sites (3), and mutation frequency increased with colony proximity to integrated steel mills (4). It was postulated that inhaled airborne contaminants emitted from steel mills, such as polycyclic aromatic compounds, were largely responsible for mutation induction; however, contaminants in the aquatic food web and differences in disease and nutritional status among gull colonies could not be eliminated as contributing factors. Therefore, the role of air pollution in producing germline mutations and the risk to humans living near steel mills could not be determined.Rodent expanded simple tandem repeat (ESTR) DNA consists of 4-to 6-bp repeat units in long tandem arrays that are unstable in the germline and tend to mutate by insertion or deletion of a number of repeat units (5-7). Laboratory studies have demonstrated that murine ESTR loci are susceptible to germline mutations induced by chemical (8) or radioactive (9, 10) mutagens, and therefore may be useful tools for environmental contamination studies. The use of sentinel laboratory animals exposed in situ is a powerful experimental approach for assessing air pollution hazards because it combines the controlled elements of laboratory studies with direct exposure to ambient pollution levels (11,12). Here, we compare germline ESTR mutation rates in laboratory mice exposed to ambient air at an industrial site near integrated steel mills to those exposed at a rural reference location, with the objective of testing inhalation of industrial air pollution as a route ...