Project 1. Sustained, high rates of production of nitric oxide (NO) by cells of the immune system, as occurs during chronic inflammation, has been strongly implicated in the development of various forms of cancer. Quantifying pathophysiological levels of NO is crucial for understanding the relationship between endogenous NO synthesis and carcinogenesis. Equally important is knowing the concentrations of reactive intermediates derived from NO, such as nitrogen dioxide (NO2), nitrous anhydride (N2O3), and peroxynitrite (ONOO-), because these species are likely mediators of damage to cells arising from NO. It is not feasible to directly measure the concentrations of any of these compounds under most conditions of interest, yet such information is needed to correlate levels of toxicity and rates of mutation in cell cultures with actual levels of exposure, and to extrapolate those findings to situations in the body. There is a need also for

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA026731-34
Application #
8567213
Study Section
Special Emphasis Panel (ZCA1-GRB-P)
Project Start
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
34
Fiscal Year
2013
Total Cost
$128,628
Indirect Cost
$51,778
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P et al. (2017) The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status. Environ Mol Mutagen 58:508-521
Fedeles, Bogdan I (2017) G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress. Proc Natl Acad Sci U S A 114:2788-2790
Chang, Shiou-Chi; Seneviratne, Uthpala I; Wu, Jie et al. (2017) 1,3-Butadiene-Induced Adenine DNA Adducts Are Genotoxic but Only Weakly Mutagenic When Replicated in Escherichia coli of Various Repair and Replication Backgrounds. Chem Res Toxicol 30:1230-1239
Chen, Fangyi; Bian, Ke; Tang, Qi et al. (2017) Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions. Chem Res Toxicol 30:1102-1110
Kimoto, Takafumi; Kay, Jennifer E; Li, Na et al. (2017) Recombinant cells in the lung increase with age via de novo recombination events and clonal expansion. Environ Mol Mutagen 58:135-145
Wang, C; Gong, G; Sheh, A et al. (2017) Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer. Mucosal Immunol 10:1504-1517
Iverson, Nicole M; Bisker, Gili; Farias, Edgardo et al. (2016) Quantitative Tissue Spectroscopy of Near Infrared Fluorescent Nanosensor Implants. J Biomed Nanotechnol 12:1035-47
Chen, Fangyi; Tang, Qi; Bian, Ke et al. (2016) Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA. Chem Res Toxicol 29:687-93
Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B et al. (2016) S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration. Proc Natl Acad Sci U S A 113:4152-7
Peng, Chunte Sam; Fedeles, Bogdan I; Singh, Vipender et al. (2015) Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity. Proc Natl Acad Sci U S A 112:3229-34

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