The identification of the neu and ras protooncogenes, the elucidation of the role of p53 tumor suppressor genes, and the sequencing of BRCA1 and BRCA2 breast cancer susceptibility genes, marked a significant breakthrough for the understanding of the genetic basis of breast cancer. Although the causes of these genetic mutations are not well understood, several factors are currently accepted as increasing the risk of breast cancer, including genetic predisposition and environmental exposure. Several chemicals commonly found in ground water and commercial procedures have been implicated in initiating a variety of cancers, including breast cancer. These chemicals include arsenic, cadmium, copper, mercury, nickel, and organophosphate pesticides. Unlike the carcinogenic nitroso compounds known to initiate and/or promote tumor formation in rodents, heavy metals and ions have been shown to cause tumors in rodents with single injections. Similarly, breast cancer, or susceptibility to it, reportedly requires decades for development. Consequently, the initiation of a sequence of mutational events, triggered by chronic, low-dose, non-carcinogenic yet toxic chemicals, may be the basis for mammary cell transformation, as recent evidence in Suffolk County (NY State) suggests. This proposal, therefore, outlines a series of experiments directed at studying mammary epithelial cells and established breast cancer cell lines using cytotoxicity testing methods and molecular biology techniques. The results will improve our understanding of the interaction between mammary cells and heavy metals and the mechanism by which these chemicals initiate mutations and allow for tumor promotion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM008153-26
Application #
6452775
Study Section
Special Emphasis Panel (ZGM1)
Project Start
2001-06-01
Project End
2002-05-31
Budget Start
Budget End
Support Year
26
Fiscal Year
2001
Total Cost
$31,452
Indirect Cost
Name
York College
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
11451
Yuan, Yiping; Shen, Xiaotong; Pan, Wei (2012) Maximum Likelihood Estimation Over Directed Acyclic Gaussian Graphs. Stat Anal Data Min 5:
Knapp, John M; Zhu, Jie S; Tantillo, Dean J et al. (2012) Multicomponent assembly of highly substituted indoles by dual palladium-catalyzed coupling reactions. Angew Chem Int Ed Engl 51:10588-91
Fearnley, Stephen Philip; Thongsornkleeb, Charnsak (2010) Oxazolone cycloadducts as heterocyclic scaffolds for alkaloid construction: synthesis of (+/-)-2-epi-pumiliotoxin C. J Org Chem 75:933-6
Macneil, Margaret A; Purrier, Sheryl; Rushmore, R Jarrett (2009) The composition of the inner nuclear layer of the cat retina. Vis Neurosci 26:365-74
Desamero, Ruel Z B; Kang, Jeonghee; Dol, Chrystel et al. (2009) Spectroscopic characterization of the SH2- and active site-directed peptide sequences of a bivalent Src kinase inhibitor. Appl Spectrosc 63:767-74
Levinger, Louis; Hopkinson, Angela; Desetty, Rohini et al. (2009) Effect of changes in the flexible arm on tRNase Z processing kinetics. J Biol Chem 284:15685-91
Zhang, Chun-Yang; Johnson, Lawrence W (2009) Single quantum-dot-based aptameric nanosensor for cocaine. Anal Chem 81:3051-5
Juszczak, Laura J; Desamero, Ruel Z B (2009) Extension of the tryptophan chi2,1 dihedral angle-W3 band frequency relationship to a full rotation: correlations and caveats. Biochemistry 48:2777-87
Arsov, I; Li, X; Matthews, G et al. (2008) BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development. Cell Death Differ 15:1385-95
Hopkinson, Angela; Levinger, Louis (2008) Effects of conserved D/T loop substitutions in the pre-tRNA substrate on tRNase Z catalysis. RNA Biol 5:104-11

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