We characterize the potential genotoxicity of compounds using various test and assays:
In vivo micronucleus test Chromosomal aberration test Traditional Ames assay
The in vivo micronucleus assay (in vivo MNT) is a reliable and commonly-employed test to meet the regulatory requirements while submitting IND, to screen the compounds (such as chemicals, impurities, pesticides, insecticides, food and feed additives) for their clastogenic potential in bone marrow of rodents (rats/mice) and as a component of exposure-based risk assessment. This assay plays a vital role in adding weight of evidence in the hazardous measurement of any chemical and quantitative risk assessments.
The Chromosomal Aberration Test (CAT) is routinely employed as part of NPD and to meet regulatory expectation to screen the compounds (such as chemicals, impurities, pesticides, insecticides, food and feed additives) for their clastogenic potential to cells (human blood lymphocytes or mammalian cell lines in culture) by evaluating the development gene/chromosome damage in the form of structural aberrations at chromosome level.
Ames test is a rapid and reliable bacterial assay used for evaluating a chemical's potential genotoxicity by measuring its ability to induce reverse mutations at selected loci of modified Salmonella and E. coli bacterial strains. These strains have various mutations and are not capable of synthesizing an essential amino acid, either histidine (Salmonella) or tryptophan (E. coli), so they can only grow in the culture medium that is supplemented with that amino acid. Once the bacteria are exposed to a mutagen, mutation(s) occur that could restore/reverse the ability of the bacteria to synthesize the amino acid and to continue growth even after depletion of traces of provided amino acid in the agar. Relevant mutations involve substitution of individual base pairs or frameshift mutations caused by addition or deletion of a stretch of DNA. The Ames test can be carried out in the presence and absence of a metabolizing system to identify potential mutagenicity by the parent compound and/or its metabolites.
Young and healthy rats/mice are exposed to the compound of interest at different concentrations derived from dose range finding study. Post treatment, animals will be euthanized and femurs are collected. Bone marrow cells from femurs are isolated and fixed on slides and then staining is performed. Four thousand polychromatic erythrocytes per each animal will be screened to measure the frequency of micronulated - polychromatic erythrocytes.
Positive results demonstrate an increase in the frequency of micronucleated polychromatic erythrocytes in treated animals which is an indication of induced chromosome damage. Increase can be statistically significant and/or dose-dependent.
Cells in cultures are exposed to the compound of interest at different concentrations for shorter duration (3-6 hours) and continuously (1.5 cell cycle time) till harvesting. In shorter duration exposure, testing will be performed by supplying liver metabolizing enzymes to evaluate by-products of compound and in other hand absence of metabolism support in shorter and continuous exposures to evaluate direct compound activity.
Positive results demonstrate an increase in the percentage of structural aberrations in comparison with concurrent controls. Increase can be statistically significant and/or dose-dependent.
For repeated and multiple screenings, we provide Mini Ames Test by using TA98/TA100/E. coli wp2 strains; Non-GLP screening assay to evaluate the multiple compounds in each step especially where test items are accessible at very less quantity.
We make the screening much more convenient by adding the one more high-throughput fluctuation assay. The extra added advantage in this service is which requires a very small amount of compound i.e. less than 50 mg. This is a 384-well plate method where Salmonella strains, TA98, TA100, TA1535, and TA1537 will be tested by exposing the test item in the exposure liquid purple color media and mutations indicated as yellow color colonies after incubation.
Quick turnaround time
Extensive experience in the genetic toxicology studies
Team of expert analytical and toxicology scientists
JULY 02, 2021
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