User:Claritycr/Genotoxicity

Project Proposal: Genotoxicity

Overview

Genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent hereditary changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis.

Mechanisms

Because the mechanisms for gene-chemical interaction are dependent on the kind of chemical and therefore varied, we will discuss several different mechanisms for interaction as subcategories here. Below is an example of a mechanism of interaction we could discuss. Obviously this isn't the full extent of what we would say, but an example of what we'll be getting at.

Particles and Fibers

The mechanisms for particles and fibers divide the effects of genotoxicity in two events: primary genotoxicity and secondary genotoxicity. Size, shape, crystallinity, and solubility properties affect primary genotoxicity; the most important factor of primary genotoxicity is the reactive oxygen species present. The persistence and extension of the reactive oxygen species leads to secondary genotoxicity. Secondary genotoxicity is believed though to have a threshold.

Techniques for Genotoxicity Tests

Short-term in vitro and in vivo tests are performed to predict the potentiality of carcinogenicity from the chemical’s genotoxic mutation. The assays are inexpensive, have high statistical power, and detect numerous amounts of end products. Some techniques commonly used are bacterial mutation assay (Ames or Salmonella assay), in vitro / in vivo cytogenetics assay, in vitro / in vivo micronucleus assay, in vitro Comet assay, and GreenScreen HC genotoxicity test. Also, genetic biomonitoring scrutinizes the genetic effects through biological monitoring in a group of individuals. With the use of predictive biomarkers, the genotoxic effects can be identified at an earlier time before other end products, such as cancer, are expressed.

Resources

http://medical-dictionary.thefreedictionary.com/genotoxicity
http://www.wisegeek.com/what-is-genotoxicity.htm
http://www.imba-research.eu/imba-workshop/presentations/17-2_meltz_genotoxicity_2006.pdf
"Genotoxicity Testing." Apredica. Cyprotex, 10 Jan. 2013. Web. 06 Feb. 2013.

Hansenne, Michel. "GENOTOXIC CHEMICALS." N.p.: n.p., n.d. N. pag. Safework Bookshelf. Web. 06 Feb. 2013.

Schins, R. P. "Mechanisms of Genotoxicity of Particles and Fibers." National Center for

Biotechnology Information. U.S. National Library of Medicine, Jan. 2002. Web. 06 Feb. 2013.

Thornton-Jones, Suzanne R. Genotoxicity Testing and Impurity Qualification. Proc. of

International Research CMC Conference. N.p.: Corporate Regulatory Affairs Sanofi- Aventis U.S., 2006. Web. 06 Feb. 2013. <http://www.iirusa.com/upload/wysiwyg/P1189/IIR_P1188_Thornton-Jones,%20Suzanne.pdf>.

The Plan

To complete the project we plan to equally participate in researching our topic. Once some mechanisms for gene-chemical interactions are agreed upon, we will likely divide up the different mechanisms and each research one or two more closely and therefore be responsible for writing that subsection. As we continue to research, more sections/subsections may become necessary to add. If so we will and divy up the work accordingly. To begin, however, we will start researching and see what presents itself within the basic structure we have outlines above.