Neoplastic transformation of breast epithelial cells by genotoxic stress

BMC Cancer

Research Article

Mahendran Botlagunta¹  Paul T Winnard¹  Venu Raman² 

[1] Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;

关键词: Tobacco Smoke;    Genotoxic Stress;    Cigarette Smoke Condensate;    Mammosphere Formation;    Breast Cancer Formation;   

DOI  :  10.1186/1471-2407-10-343

 received in 2009-08-31, accepted in 2010-06-30,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundExposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation and progression of breast cancer. The combination of these two genotoxic insults can induce significant damage to the genetic material of the cells resulting in neoplastic transformation.MethodsTo study the effects of low dose ionizing radiation and tobacco smoke on breast cells, MCF 10A cells were treated either with radiation (Rad - 0.1 Gray) or cigarette smoke condensate (Csc - 10 microgram/ml of medium) or a combination of Rad + Csc. Following treatments, cells were analyzed for cell cycle distribution patterns and the ability to extrude the Hoechst 33342 dye. In addition, in vitro invasion and migration as well as mammosphere formation assays were performed. Finally, differential gene expression profiles were generated from the individual and combination treatment.ResultsExposure of MCF 10A cells to the combination of radiation plus cigarette smoke condensate generated a neoplastic phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases with a doubling of the population in S phase, and increased invasion and motility. Also, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. In addition, changes in gene expression include the up regulation of genes encoding proteins involved in metabolic pathways and inflammation.ConclusionsThe results indicate that when normal breast cells are exposed to low dose radiation in combination with cigarette smoke condensate a phenotype is generated that exhibits traits indicative of neoplastic transformation. More importantly, this is the first study to provide a new insight into a possible etiology for breast cancer formation in individuals exposed to low dose radiation and tobacco smoke.

【 授权许可】

Unknown   
© Botlagunta et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.