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T09002: Cellular and genomic responses to toxicology
Thursday 14 October 2004
This research project aims to improve our understanding of how one group of harmful chemicals sometimes found in food may cause cancer.
Study Duration
: January 2000 to September 2003
Contractor
: Imperial College
Background
The aim of this project was to investigate possible links between one type of food component and the development of diet related-cancer.
Research Approach
The project examined the way a known chemical carcinogen (benzo[a]pyrene), sometimes present as a contaminant in food, altered the way human cells functioned.
The study looked in detail at the changes in the levels of specific genes and proteins in the cells in response to exposure to this chemical.
Results and findings
The researchers found that benzo[a]pyrene increased the level of some genes and proteins involved in the metabolism of chemicals, and decreased the level of genes that regulate cell growth and division. These responses may be associated with the mechanisms by which benzo[a]pyrene produces its toxic effects.
Published papers
Published papers:
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Zhu H and Gooderham NJ, (2001). P450 1A1 dependent and independent effects of benzo[a]pyrene in human lung fibroblast MRC-5 SV2 cells. Toxicology, 164, 155.
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Zhu H and Gooderham NJ, (2001). P450 1A1 dependent induction of morphological transformation by benzo[a]pyrene in human lung fibroblast MRC-5 SV2 cells. Mut. Res., 483, S131.
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Zhu H and Gooderham NJ, (2001). Simultaneous stimulation of growth, apoptotic death and gene mutation by benzo[a]pyrene in human lung fibroblast MRC-5 SV2 cells. Proc. Am. Assoc. Cancer Res., 42, 471.
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Gooderham NJ, Zhu H, Lauber S, Boyce A and Creton S, (2002). Molecular and genetic toxicology of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Mut. Res., 506, 91-9.
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Zhu H. and Gooderham NJ, (2002). Induction of neoplastic phenotype in MRC-5SV2 human lung fibroblast cells by benzo(a)pyrene is preceded by DNA ploidy changes. Human Genome Meeting, 100.
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Zhu H and Gooderham NJ, (2002). Neoplastic transformation of human lung fibroblast MRC-5 SV2 cells induced by benzo[a]pyrene and confluence culture. Cancer Res., 62, 4605-9.
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Zhu H, Smith C, Ansah C and Gooderham NJ, (2005). Responses of genes involved in cell cycle control to diverse DNA damaging chemicals in human lung adenocarcinoma A549 cells. Cancer Cell Int., 5, 1-13.
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