Description: To develop a test of a new method of indoor allergen collection that is less cumbersome, less costly and more easily performed at remote sites than the current method. First a method will be designed and validated using wipes, in 50 households already being tested for antigens in the USC Children’s Health Center Asthma Intervention Study. Levels of dust mites, cockroaches, and cat dander antigens (Der P 1, Der F 1, Bla g 1, and Fel D 1) in the wipes will be analyzed by Dr. Davaid Diaz-Sanchez using standardized ELISA methods. These results will be compared to results obtained using a standardized vaccuum collection method already in place. If the correlation between the two methods is good (r=0.75 or above), we will identify 25 twins from the California Twin Program and test the effectiveness of the wipe test as a self-administered, remote allergen collection method. Twins offer an ideal population in which to study gene-environmental interaction.

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Description: Recent epidemiologic results have linked slower lung function growth rates among California school children to increased ambient exposures of respirable particles, acid vapor, and nitrogen dioxide. These pollutants are highly inter-related and collectively represent a combination of mobile source emissions and atmospheric reactions. To develop a well-constructed project that might separate the relative contribution of these pollutants to observed health outcomes, we propose to assess the intra-community variability of a surrogate pollutant for motor vehicle emissions (nitrogen dioxide-NO2). Passive NO2 samplers (Palmes tubes) will be deployed across three California communities currently participating in a multi-year health studies. Samplers will be deployed on two separate occasions in each of the communities to assess intra-community variability for sampling periods of two weeks duration. Samplers will be deployed at the community monitoring station, at local high schools, outside homes of students participating in the longitudinal health investigation, and at other key locations at discrete distances from major traffic arteries. The data will be analyzed to assess the relative intra-community NO2 variability, whether the central community monitoring site adequately describes exposure for the surrounding community, and to determine the optimal deployment pattern for subsequent larger-scale investigations of pollutant spatial variability within study communities.

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Description: This pilot proposal investigates the kinetic mechanisms governing the incorporation of nucleotides opposite damaged DNA template bases, and translesion synthesis, by a new class of errant DNA polymerases spanning prokaryotic and eucaryotic organisms, the UmuC/DinB/Rev1/Rad30 superfamily of polymerases. Our focus is on lesions implicated in causing mutations and cancer in model animal systems and humans. Examples of the lesions to be studied include alkylated bases (e.g., O6AlkG, O2AlkT, O4AlkT), UV-damaged gases (cis-syn TT dimers, 7-4 TT photoproducts), abasic moieties, and polycyclic aromatic hydrocarbons (BPDE isomers). We propose to use a gel kinetic fidelity assay developed in our laboratory to measure the specificity of nucleotide incorporation and efficiency of translesion synthesis with a variety of error-prone DNA polymerases and accessory proteins. There are two overriding objectives: the first is to determine nucleotide incorporation specificities in various template sequence contexts and to compare them with in vivo mutational hot spots; the second is to investigate the mechanisms used by this new class of errant polymerases to diminish the fidelity of DNA synthesis and thereby generate efficient translesion synthesis (TLS). We have chosen to focus our discussion in the proposal on one of the most onerous group of DNA damage compounds, the class of polycyclic aromatic hydrocarbons (PAHs). The concepts and techniques described, however, carry over completely to encompass essentially all classes of bulky and non-bulky DNA adducts.

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