Imperial College London
Alternate

Emeritus ProfessorNigelGooderham

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Emeritus Professor of Molecular Toxicology
 
 
 
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Contact

 

n.gooderham Website

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Malik:2018:10.1007/s00204-018-2291-z,
author = {Malik, D-E-S and David, RM and Gooderham, NJ},
doi = {10.1007/s00204-018-2291-z},
journal = {Archives of Toxicology},
pages = {3223--3239},
title = {Mechanistic evidence that benzo[a]pyrene promotes an inflammatory microenvironment that drives the metastatic potential of human mammary cells},
url = {http://dx.doi.org/10.1007/s00204-018-2291-z},
volume = {92},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Benzo[a]pyrene (B(a)P) is a major cancer-causing contaminant present in food such as cooked meats and cereals, and is ubiquitous in the environment in smoke derived from the combustion of organic material. Exposure to B(a)P is epidemiologically linked with the incidence of breast cancer. Although B(a)P is recognized as a complete genotoxic carcinogen, thought to act primarily via CYP-mediated metabolic activation to DNA-damaging species, there is also evidence that B(a)P exposure elicits other biological responses that promote development of the cancer phenotype. Here in mechanistic studies using human mammary cells MCF-7 and MDA-MB-231, we have explored mechanisms whereby B(a)P (10- 8 to 10- 5M) promotes inflammation pathways via TNF-α and NFκB leading to IL-6 upregulation, microRNA (Let7a, miR21 and miR29b) dysregulation and activation of VEGF. The miRNA dysregulation is associated with altered expression of inflammation mediators and increased migration and invasive potential of human mammary cancer cells. Our data suggest that mammary cell exposure to B(a)P results in perturbation of inflammation mediators and dysregulation of tumorigenic miRNAs, leading to an inflammation microenvironment that facilitates migration and invasion of mammary epithelial cells. These properties of B(a)P, together with its well-established metabolic activation to DNA-damaging species, offer mechanistic insights into its carcinogenic mode of action.
AU  - Malik,D-E-S
AU  - David,RM
AU  - Gooderham,NJ
DO  - 10.1007/s00204-018-2291-z
EP  - 3239
PY  - 2018///
SN  - 0340-5761
SP  - 3223
TI  - Mechanistic evidence that benzo[a]pyrene promotes an inflammatory microenvironment that drives the metastatic potential of human mammary cells
T2  - Archives of Toxicology
UR  - http://dx.doi.org/10.1007/s00204-018-2291-z
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30155724
UR  - http://hdl.handle.net/10044/1/63537
VL  - 92
ER  -
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