HUMAN PERIPHERAL BLOOD STUDIES OF MUTATIONS IN THE ABERJONA REGION

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Description: The chemical analysis of sediment cores in the peat marsh near municipal wells G and H confirmed by similar analysis in the Upper Mystic Lake indicates that a massive bolus of heavy metals including chromium and arsenic passed by the well sites sometime after the early 1960's. Hydrogeologic models show that some 60% of the water drawn from wells G and H water drawn in the summers of 1964 to 1979 had to come from the Aberjona River. Based on the sedimentary record estimated flow rates and modelling of local conditions, it is calculated that chromium and arsenic concentrations of 200 mug/L and 50 mug/L respectively were present in the drinking water of East Woburn. This is equivalent to 4muM chromate which was found to be markedly mutagenic to human cells in a 5 hour exposure. The mutational spectrum of this treatment has been determined in exon 3 of the human hprt gene in vitro. It is now proposed to study the mutational spectra in blood cells sampled from residents of East Woburn, West Woburn, Arlington and West Medford to discover if the genetic effects of chromium may be found in exposed residents. Before this, it is proposed that samples of childhood hair be collected for analysis to discover if and when exposure occurred. Given confirmatory results, they will use their community outreach effort to explain the goals, methods and limitations of their technology. They propose to enroll five multi-generational families who collectively represent persons of both genders, a wide distribution of ages and European and African ancestry. In particular two families living primarily in East Woburn 1960-1990 will be sought whose source of drinking water was the municipal water supply. In parallel with this public education and solicitation effort they propose to pursue certain additional technical goals which are needed for facile and accurate mutational spectrometry in human blood samples. These involve improved methods for sample preparation, exploration of certain multicopy nuclear DNA sequences for suitability, development of internal standards and development of laboratory protocols to assure quality, accuracy and donor confidentiality. Initially they propose to obtain some fifty mutational spectra from fifty donors. They hope to be able to discern if the mutational spectrum of chromate is present in the DNA samples of persons who consistently drank water from wells G and H and not present in unexposed individuals. They then hope to see if there are differences among spectra within families on the basis of age or gender; they then hope to be able to discover if there are significant differences within or among families in our studies. If successful, they will have laid the basis for a new and valuable way to discover the amount and kinds of mutations in human populations and offer the means to identify environmental causes, if any, of genetic change in humans.