Abstract

The overall objectives of our research are to determine what role, if any, nitrite and nitroso compounds play in the etiology of human cancer. The main focus of the Program will be concerned with exploring and testing the hypothesis that endogenous factors are important in either causation or modification of the process of carcinogenesis in humans. Project 1 will investigate how different types of cells make nitric oxide from arginine. Nitric oxide is the reactant which yields the nitrosating agents N2O3 and N2O4 in the presence of O2. Project 2 proposes several animal models in which infectious agents lead to increased risk of cancer. Both gastric cancer and liver cancer will be investigated as models in which nitrogen oxides may play a role. Project 3 will investigate the role of somatic mutations in ras genes, the inactivation of the P53 gene and the occurrence of the TPR-MET oncogene rearrangement in experimental gastric carcinogenesis. Project 4 will investigate the pharmacokinetics of dimethylamine and trimethylamine; the aqueous chemistry of nitric oxide; and the formation of nitrosamines from nitric oxide. Project 5 will examine the chemistry of indole nitrosation products and their reactions with DNA and the potential for reactions between nitrogen oxides and DNA. Each project explores basic mechanisms of endogenous carcinogenesis and the Program as a whole may lead to new directions in the prevention of cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA026731-12
Application #
3093147
Study Section
Special Emphasis Panel (SRC (D1))
Project Start
1980-03-01
Project End
1994-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Other Domestic Higher Education
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Gu, Chen; Ramos, Jillian; Begley, Ulrike et al. (2018) Phosphorylation of human TRM9L integrates multiple stress-signaling pathways for tumor growth suppression. Sci Adv 4:eaas9184
Wadduwage, Dushan N; Kay, Jennifer; Singh, Vijay Raj et al. (2018) Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Sci Rep 8:12108
Tajai, Preechaya; Fedeles, Bogdan I; Suriyo, Tawit et al. (2018) An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity. Free Radic Biol Med 116:64-72
Rothenberg, Daniel A; Taliaferro, J Matthew; Huber, Sabrina M et al. (2018) A Proteomics Approach to Profiling the Temporal Translational Response to Stress and Growth. iScience 9:367-381
Wang, Xin; Garcia, Carlos T; Gong, Guanyu et al. (2018) Automated Online Solid-Phase Derivatization for Sensitive Quantification of Endogenous S-Nitrosoglutathione and Rapid Capture of Other Low-Molecular-Mass S-Nitrosothiols. Anal Chem 90:1967-1975
Chan, Cheryl; Pham, Phuong; Dedon, Peter C et al. (2018) Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol 19:228
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
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
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
Edrissi, Bahar; Taghizadeh, Koli; Moeller, Benjamin C et al. (2017) N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats. Chem Res Toxicol 30:1572-1576

Showing the most recent 10 out of 361 publications