This Program links basic research in analysis of public health records, measurement of mutations and cell kinetics in dissected human lungs, studies of the mutagenic effects of airborne toxicants at dose levels mimicking the human lung, measurement of the broad set of DNA adducts, derived from airborne toxicants and analysis of particle in human lungs and the study of the sources and basic mechanisms of formation of the primary human cell mutagens found in urban air. Together we are testing the hypothesis that exposure to combustion generated airborne toxicants mutate or otherwise change the cell kinetic behavior of human lung cells so the rate of lung cancer is increased in the American population.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Program Projects (P01)
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Special Emphasis Panel (ZES1-DPB-A (P))
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Velazquez, Jose M
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Massachusetts Institute of Technology
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Zheng, Weiming; Khrapko, Konstantin; Coller, Hilary A et al. (2006) Origins of human mitochondrial point mutations as DNA polymerase gamma-mediated errors. Mutat Res 599:11-20
Coller, Hilary A; Khrapko, Konstantin; Herrero-Jimenez, Pablo et al. (2005) Clustering of mutant mitochondrial DNA copies suggests stem cells are common in human bronchial epithelium. Mutat Res 578:256-71
Pedersen, Daniel U; Durant, John L; Taghizadeh, Koli et al. (2005) Human cell mutagens in respirable airborne particles from the northeastern United States. 2. Quantification of mutagens and other organic compounds. Environ Sci Technol 39:9547-60
Pedersen, Daniel U; Durant, John L; Penman, Bruce W et al. (2004) Human-cell mutagens in respirable airborne particles in the northeastern United States. 1. Mutagenicity of fractionated samples. Environ Sci Technol 38:682-9
Tomita-Mitchell, Aoy; Ling, Losee Lucy; Glover, Curtis L et al. (2003) The mutational spectrum of the HPRT gene from human T cells in vivo shares a significant concordant set of hot spots with MNNG-treated human cells. Cancer Res 63:5793-8
Luo, Wen; Gurjuar, Rajan; Ozbal, Can et al. (2003) Quantitative detection of benzo[alpha]pyrene diolepoxide-DNA adducts by cryogenic laser induced fluorescence. Chem Res Toxicol 16:74-80
Kim, Andrea S; Thilly, William G (2003) Ligation of high-melting-temperature 'clamp' sequence extends the scanning range of rare point-mutational analysis by constant denaturant capillary electrophoresis (CDCE) to most of the human genome. Nucleic Acids Res 31:e97
Muniappan, Brindha P; Thilly, William G (2002) The DNA polymerase beta replication error spectrum in the adenomatous polyposis coli gene contains human colon tumor mutational hotspots. Cancer Res 62:3271-5
Kim, Andrea S; Holmquist, Gerald P; Thilly, William G (2002) High-efficiency DNA ligation for clamp attachment without polymerase chain reaction. Anal Biochem 310:179-85
Zheng, Weiming; Marcelino, Luisa A; Thilly, William G (2002) Scanning low-frequency point mutants in the mitochondrial genome using constant denaturant capillary electrophoresis. Methods Mol Biol 197:93-106

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