Genetic toxicology

Genetic toxicology aims to determine whether or not a given compound will induce mutations or chromosomal damage in humans. Today, new insights into the mechanisms of mutagenicity has opened up new possibilities for testing and predicting mutagenicity.

For more than 40 years, ERBC scientists conduct standard screening and regulatory assays as well as customized testing strategies to accurately assess the genotoxicity risk of any compounds (pharmaceutical ingredients, pharmaceutical impurities, human metabolites and chemicals) and help pharmaceutical and chemical companies to take better account of ICH-and OECD guidelines They also support studies lead by other safety assessment internal teams through genetic toxicology biomarkers and mechanistic explorations.

Bacterial tests in vitro

Bacterial mutation assay
Photogenotoxicity – Ames Test

Mammalian tests in vitro

Gene mutation in Chinese hamster V79 cells (HPRT)
Mutation in L5178Y TK+/- mouse lymphoma cells (fluctuation method)
In vitro chromosome aberrations in Chinese hamster cells (V79 CHO) and human lymphocytes
In vitro micronucleus test on human lymphocytes or Chinese hamster cells (V79 CHO)

Mammalian tests in vivo

In vivo micronucleus test (single dose or multiple dose) in mouse and rat
In vivo chromosomal aberration test (single dose or multiple dose) in rat
Unscheduled DNA synthesis (UDS) in primary rat hepatocytes after in vivo treatment
In vivo comet assay in rat
Combined comet assay and micronucleus test after repeated dosing in rat

Preliminary genotoxicity assessment

Screening for lead compound identification using standard and miniaturized methods:

Modified 6-well bacterial mutation assay
In vitro micronucleus test in Chinese hamster cells (V79 CHO) or mouse lymphoma cells
In vitro comet assay on human leukocytes, Chinese hamster cells (V79 CHO) or mouse lymphoma cells

Mechanistic studies

Oxidative stress: determination of 8-OH-dG (8-oxo-7,8-dihydro-2’deoxyguanosine) by LC/MS after in vivo or in vitro treatment
Replicative DNA Synthesis study (RDS) in primary rat hepatocytes after in vivo treatment
Inhibition of topoisomerase II
Stabilization of cleavable complex (in vitro chromosome aberration assay)