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An Introduction to Genetic Toxicology

by Constantine on November 23, 2012

This is the first of a series of posts that will serve as an introduction to some of the services that we offer and which cover some of the most common requests that we receive here at Nucro-Technics.

Developing drugs is an expensive and time consuming process.  Timelines for the development of a new drug can stretch past a decade, with costs entering the billions.  A large part of the time and money spent developing new drugs is used developing several candidates for the same use, not all of which will turn out to be viable.  Genetic toxicology testing can help narrow down the list of potential candidates by eliminating drugs that have a high cancer-causing potential.  These tests can be performed relatively cheaply and quickly, thus saving drug development companies precious time and resources that could be better spent on developing successful and safe drug candidates.

Over the past 40 years, efforts have been made to pre-emptively determine the cancer-causing effects of drugs and chemicals before they are put on the market.  Currently the FDA requires a battery of tests to evaluate the cancer-causing potential of a drug or controlled substance before it goes to market.  These genetic toxicology tests determine whether and how substances cause damage or mutations in DNA and genes, which could lead to cancer.  At Nucro-Technics, we offer a full range of FDA and Health-Canada approved genetic toxicology tests with a range of prices and turn-around times.

There are three components to the FDA-required genetic toxicology test battery.  The first is a simple test to see if mutations occur in bacterial DNA, called the Ames test.  Because mutations in DNA often lead to cancer, signs of mutation in this test are a good preliminary indicator of the carcinogenic properties of a compound, or its metabolites.  The Ames test includes testing on 5 bacterial strains and has a turn-around time of about 8 weeks.  Alternatively, we can perform a quicker 2 strain screen if the customer indicates so.

The second component of the FDA-required genetic toxicology test battery involves in vitro studies of the carcinogenic effects of a compound on mammalian cells.  Nucro-Technics offers three tests in this category, all of which have a turn-around time of about 3 months.  The first test is called chromosome aberration, which tests the ability of a compound to cause large structural breaks in the chromosomes of mammalian cells.  The second test is called In Vitro Micronucleus Testing.  This test can determine if chemicals are causing breaks or changes in numbers of chromosomes.  The third test, which is preferred by the FDA, is called the Mouse Lymphoma Assay.  This test can determine a broad spectrum of gene mutations that may lead to cancer.

The final component of the FDA-required genetic toxicology test battery involves in vivo genetic toxicology studies in mammals.  These studies differ from the in vitro tests in that they assess the cancer causing potential of a substance on a whole organism, as opposed to applying the substance directly to cells.  These studies are very comprehensive and involved and can take up to three months to complete.  These studies, the micronucleus and chromosomal aberration tests, both are performed in the bone marrow of mice.  Bone marrow is used because it contains many rapidly dividing cell types which are targets for many types of cancer.

Currently, the FDA requires these tests to be carried out as multi-test batteries.  The first option is to have a test from each component (e.g. Ames test, in vitro chromosomal aberration, in vivo mouse micronucleus) or an Ames test and two in vivo tests.  By performing this battery of tests, the carcinogenic potential of a substance is adequately addressed.

There are several alternatives to these tests available.  First, a carcinogenicity study can be performed.  These studies involve dosing animals (typically rats or mice) with a substance, and monitoring them over a two year period to see if they develop tumors.  By using p53-knockout mice instead, the study time can be shortened to just 6 months, which is still double the length of the longest of the FDA approved battery tests.  Second, compounds can be analyzed by computational models to see if they possess classical markers of carcinogenicity.  This new and emerging field will provide fast and valuable information on carcinogenicity, without the delay times or animal use of other studies.

In addition to offering these services, Nucro-Technics offers many other related tests.  We can assess the photomutagenicity and phototoxicity of a compound.  These tests study the cancer causing potential of a substance when it is exposed to light (visible and UV light is used).  Also, we can determine if a substance, such as a cancer treatment drug, is effective for killing cancer cells.  We offer the following cytotoxicity studies – Neutral Red Assay (determines lysosomal integrity), Extracellular Lactate Dehydrogenase (checks for plasma membrane damage), Tetrazolium Salt (reports mitochondrial function) and Cleaved Caspase-3 Detection (quantifies apoptosis).

For more information on any of these genetic toxicology tests that Nucro-Technics offers, please feel free to explore the Genetic Toxicology section of our website.  To receive a quotation, or to schedule a test, please contact NUCRO-TECHNICS directly.

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