Overall objectives: The Core Laboratory in Analytical Chemistry is the chemical analysis arm of the Center for Environmental Health Sciences. It is a central resource in analytical chemistry for Program Project participants, providing them with analytical expertise, training, and access to analytical instrumentation. A major CEHS goal is to foster collaborative research among combustion engineers, genetic toxicologists, analytical chemist, civil engineers and other investigators in order to solve important problems in human health effects research. The Core Lab in Analytical Chemistry is an important resource in making this research collaboration come to fruition.
Specific aims : The Core Lab in Analytical Chemistry, operating in conjunction with the Core Lab in Toxicology, will work closely with the Project 1 research team (Sarofim, Howard, Cass) and Project 2 research team (Thilly, Crespi, Willey) to determine the most important human cell mutagens (MIMs) in ambient air samples from Los Angeles, CA; Woburn, MA; and Rochester, NY. In order to accomplish this objective, protocols based on bioassay-directed chemical analysis will be used. Relevant analytical methods and separation procedures will be developed and tested. When MIMs are identified, additional effort to determine their combustion sources and formation mechanisms will be initiated in collaboration with Project 1 Investigators. Relevance to human health: It is CEHS and Core Lab policy to focus major efforts on samples whose presence in the biosphere is likely to pose a threat to human health. To date, much of our work has focused on the characterization of polycyclic aromatic hydrocarbons (PAH) and derivatives emitted into the environment by combustion systems and on chemical emanating from Superfund sites in a nearby watershed. In the present Program, we will focus on the characterization of airborne chemicals because of (a) the observed urban excess of lung cancer, (b) clear human cell mutagenicity of airborne chemicals, (c) finding of PAH adducts in human lungs at mutagenic levels, and (d) the appearance of oncomutations in lung cancers of the kind associated with PAH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
1P01ES007168-01
Application #
3755343
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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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