Application Note: Early detection of Genotoxicity: Integrated Services from Gentronix
25 August 2011

Testing for genotoxicity is a regulatory requirement, historically conducted late in the preclinical phase of drug development. Such testing using the regulatory battery of tests is time consuming and costly with positive results leading to delays or even termination of development. Gentronix provides a comprehensive early genotoxicity screening using cell based assays and in vitro genotoxicity assays.

GreenScreen HC and BlueScreen HC 

Early accurate screening conducted with GreenScreen® HC or BlueScreen HC™ human (TK6) cell based assays gives rapid results. Both assays use patented gene reporter systems with either Green Fluorescent Protein (GFP) or Gaussia Luciferase (G.Luc) to detect up-regulation of GADD-45a, a key P53 dependant response element in the DNA stress pathway. The assays require only milligram quantities of material and give results in just 48hrs.

In vitro Micronucleus Test

The micronucleus assay detects aberrant, small nuclei present in the cell cytoplasm. Micronuclei may contain whole chromosomes ‘lost’ during mitosis or fragments generated by chromosome breakage.

Flow cytometric assessment permits automated scoring, which removes subjectivity, and rapid measurement of large numbers of cells increases statistical power. In addition, the in vitro MicroFlow® method used by Gentronix allows simultaneous collection of relative survival and membrane integrity parameters for cytotoxicity assessment, as well as cell cycle information. 

Ames MPF assay
Ames MPF™ is an adapted microfluctuation method for performing the Ames bacterial mutagenicity test. Hisˉ or Trpˉ tester strains are incubated with test samples and scored for colony growth, indicating reversion to His+ or Trp+ phenotype has occurred. In this liquid format of the test, small cultures are scored in 384-well microplates using an indicator medium colour change (purple to yellow). A test agent is assayed across 6 dose levels with concurrent zero dose and positive controls, all performed in triplicate to provide statistical robustness.

In vitro COMET assay

The Comet assay, also called single cell gel electrophoresis, is a technique used for the sensitive detection of DNA damage in individual cells following exposure to a test compound. 

For a comprehensive guide please visit the company article page.