Abstract

This program of research concerns the chemistry of food-borne environmental toxicants; characterization of their mutagenicity to Salmonella typhimurium and to human lymphoblasts and their carcinogenicity to rodents; and experiments relating to their metabolism, interactions with cellular macromolecules, and mechanisms of action. Projects relating to chemistry involve studies of formation and detection of N-nitroso compounds and hydroxamates; products of pyrolysis of amino acids, proteins and other food materials; and reaction products of peroxidizing lipids and cholesterol oxidation. Metabolism of quercetin and other flavonols as well as amino acid pyrolysis products will be studied. Experiments on mode of action include isolation and identification of DNA adducts; quantitative and kinetic features of their levels in relation to mutagenesis and carcinogenesis; synthesis of DNA fragments containing adducts and their involvement in mutational events; effects of DNA damaging agents of the structure of E. coli DNA; and effects of chemical-macro molecular interactions on nucleolar structure and function in rat liver nuclei. Further studies are designed to determine the influence of diet composition on carcinogenicity of amino acid pyrolysis products; and detection of DNA damage caused by carcinogens in tissues of rats.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
2P01ES000597-16
Application #
3095773
Study Section
Environmental Health Sciences Review Committee (EHS)
Project Start
1976-04-01
Project End
1991-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
16
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Larson, P S; McMahon, G; Wogan, G N (1993) Modulation of c-myc gene expression in rat livers by aflatoxin B1 exposure and age. Fundam Appl Toxicol 20:316-24
Tannenbaum, S R; Skipper, P L; Wishnok, J S et al. (1993) Characterization of various classes of protein adducts. Environ Health Perspect 99:51-5
Soman, N R; Wogan, G N (1993) Activation of the c-Ki-ras oncogene in aflatoxin B1-induced hepatocellular carcinoma and adenoma in the rat: detection by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A 90:2045-9
Keohavong, P; Ling, L; Dias, C et al. (1993) Predominant mutations induced by the Thermococcus litoralis, vent DNA polymerase during DNA amplification in vitro. PCR Methods Appl 2:288-92
Oleykowski, C A; Mayernik, J A; Lim, S E et al. (1993) Repair of aflatoxin B1 DNA adducts by the UvrABC endonuclease of Escherichia coli. J Biol Chem 268:7990-8002
Sheabar, F Z; Groopman, J D; Qian, G S et al. (1993) Quantitative analysis of aflatoxin-albumin adducts. Carcinogenesis 14:1203-8
Keohavong, P; Thilly, W G (1992) Determination of point mutational spectra of benzo[a]pyrene-diol epoxide in human cells. Environ Health Perspect 98:215-9
Keohavong, P; Thilly, W G (1992) Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. Proc Natl Acad Sci U S A 89:4623-7
Groopman, J D; Hasler, J A; Trudel, L J et al. (1992) Molecular dosimetry in rat urine of aflatoxin-N7-guanine and other aflatoxin metabolites by multiple monoclonal antibody affinity chromatography and immunoaffinity/high performance liquid chromatography. Cancer Res 52:267-74
Wogan, G N (1992) Aflatoxins as risk factors for hepatocellular carcinoma in humans. Cancer Res 52:2114s-2118s

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