Neoplastic transformation of breast epithelial cells by genotoxic stress

Abstract

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.

Radiation-induced DNA Double Strand Breaks and Their Modulations by Treatments with <em>Moringa oleifera</em> Lam. Leaf Extracts: A Cancer Cell Culture Model

“…Cells also appeared more rounded with increasing radiation dose. These observations were similar to what had been previously reported on irradiated MCF-7 and normal breast epithelial cells [9,10]. Alteration in plasma membrane morphology and reorganization of actin filament close to the plasma membrane had also been reported.…”

Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells

“…The response of breast epithelial cells and breast cancer cell to cigarette smoke has been previously examined [15,16,30,31], but these studies focused on short-term treatment (up to one week) while we have analyzed the effect of continuous long-term exposure. We demonstrated that chronic exposure to tobacco smoke in the form of CSE or CSC can alter the phenotype of mammary epithelial cells, promoting the acquisition of mesenchymal traits such as increased anchorage-independent growth, motility, invasion, and the expression of markers associated with self-renewal and tumor initiation.…”

NZ51, a ring-expanded nucleoside analog, inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3

“…One such agent is the environmental pollutant, benzo[a]pyrene diol epoxide (BPDE), which can form stable DNA adducts [ 5 – 7 ]. Previously, our laboratory reported the oncogenic role of BPDE in human breast epithelial cells [ 8 ] and identified an RNA helicase, DDX3X (DDX3), as a contributing factor [ 9 ]. We demonstrated that DDX3 was upregulated after exposing immortalized non-tumorigenic breast epithelial cells, MCF 10A, to BPDE.…”