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The Interactive and Carcinogenic Effects of Hexavalent Chromium and Arsenic in Human Lung Cells

EPA Grant Number: F07D91105
Title: The Interactive and Carcinogenic Effects of Hexavalent Chromium and Arsenic in Human Lung Cells
Investigators: Holmes, Amie L.
Institution: University of Southern Maine
EPA Project Officer: Willett, Stephanie H.
Project Period: September 1, 2007 through September 1, 2010
RFA: GRO Graduate Fellowships (2007)
Research Category: Fellowship - Toxicology , Health Effects , Academic Fellowships

Description:

Objective:

Hexavalent chromium (Cr(VI)) and arsenic are two dangerous environmental pollutants, because they are known human lung carcinogens and exposure is widespread. However, their carcinogenic mechanisms remain unknown and even less is known about their interactions. Interactions between these two metals are likely because both are common drinking water contaminants, and chromate is a known contaminant in cigarette smoke. Since potential exposure to Cr(VI) and arsenic is high, it is important to understand the mechanisms involved in their carcinogenic potential and their potential interactions.

The objective of this research project is to develop a model demonstrating the interactions between environmental contaminants by specifically examining the co-interactions of chromate and arsenic and determining if arsenic potentiates the carcinogenicity of Cr(VI).

Approach:

Human bronchial cells will be used as a model to assess the interactions between Cr(VI) and arsenic. Cells will be co-treated with varying concentrations of soluble or particulate Cr(VI) and arsenic and various endpoints will be studied. First, centrosome amplification and chromosome instability will be assessed using immunocytochemistry and the aneuploidy assay, respectively. The next step will be to determine the effects of co-exposure on neoplastic transformation using the transformation assay which detects loss of contact inhibition and anchorage independent growth. Lastly, microarrays will be used to determine if arsenic alters Cr(VI)-induced gene expression in centrosome regulated genes.

Expected Results:

Our laboratory has shown that chronic exposure to Cr(VI) induces centrosome amplification and chromosome instability. It is expected that arsenic will significantly increase the amount of cells with Cr(VI)-induced centrosome amplification and chromosome instability by inhibiting the spindle assembly checkpoint. Therefore, co-exposure to arsenic will also increase the carcinogenicity of Cr(VI) and alter the expression of centrosome regulated genes and spindle assembly checkpoint genes. When completed, this research will provide a better understand of how arsenic and chromate interact to cause cancer; essential information to better assess the relative risk of exposure to As and Cr(VI); and a model of chemical interactions in human lung cells for further study of interactions between and among other environmental contaminants.

Supplemental Keywords:

chromium, arsenic, chromosome instability, centrosome amplification, transformation,

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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