It is a central theme of this Program Project that inflammation causes cancer. We strive to understand how it causes cancer, particularly cancers of the gastrointestinal tract, because understanding the chemical and molecular steps underlying the mechanism of neoplastic transformation provides valuable insight into the biology of end stage cancers. Moreover, this mechanistic understanding identifies steps at which intervention in terms of therapy or prevention strategies is likely to reduce disease burden in humans. Project 2 integrates with Project 1, which identifies a population of chemical mediators that in aggregate represent the drivers of the genetic changes many researchers believe underpin the conversion of normal cells into cancer cells. These

Public Health Relevance

This Project utilizes unique chemical and genetic tools to uncover the type, amount and genetic requirements for the inflammation-induced local mutations and DNA strand breaks that presumably initiate and help drive the process of carcinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA026731-35A1
Application #
8666941
Study Section
Special Emphasis Panel (ZCA1-RPRB-B (J1))
Project Start
1997-01-15
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
35
Fiscal Year
2014
Total Cost
$186,571
Indirect Cost
$66,974
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142
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
Chang, Shiou-chi; Fedeles, Bogdan I; Wu, Jie et al. (2015) Next-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo. Nucleic Acids Res 43:5489-500
Shen, Zeli; Feng, Yan; Rickman, Barry et al. (2015) Helicobacter cinaedi induced typhlocolitis in Rag-2-deficient mice. Helicobacter 20:146-55
Fedeles, Bogdan I; Freudenthal, Bret D; Yau, Emily et al. (2015) Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer. Proc Natl Acad Sci U S A 112:E4571-80
Singh, Vipender; Fedeles, Bogdan I; Essigmann, John M (2015) Role of tautomerism in RNA biochemistry. RNA 21:1-13
Chan, Clement T Y; Deng, Wenjun; Li, Fugen et al. (2015) Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective Expression of Codon-Biased Genes. Chem Res Toxicol 28:978-88
Iverson, Nicole M; Strano, Michael S; Wogan, Gerald N (2015) In Vivo Delivery of Nitric Oxide-Sensing, Single-Walled Carbon Nanotubes. Curr Protoc Chem Biol 7:93-102
Zeiger, Errol; Gollapudi, Bhaskar; Aardema, Marilyn J et al. (2015) Opportunities to integrate new approaches in genetic toxicology: an ILSI-HESI workshop report. Environ Mol Mutagen 56:277-85
Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner et al. (2015) Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet 11:e1004901

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