In Vitro Genotoxicity

Creative Bioarray offers a series of genotoxicity tests to identify chemicals that can cause genetic alterations in cells following the OECD test guidelines, including bacterial reverse mutation test OECD 471 (also known as Ames test), in vitro mammalian chromosomal aberration test OECD 473, in vitro mammalian cell micronucleus test OECD 487, in vitro gene mutation assays OECD 490, as well as other genotoxicity assays such as in vitro comet assay and genotoxicity screening.

Genotoxicity, compared to other types of toxicity, may result in severe consequences that can be amplified and inherited after exceptionally long periods following exposure. Even DNA damage that occurs in a single cell caused by genotoxic drugs at low exposure can cause unexpected severe consequences in the long run.

Genotoxicity includes mutagenicity that involves alterations in the DNA structure, as well as DNA damage that may not result in permanent alterations in the DNA structure. Therefore, genotoxicity studies include tests that detect gene mutations, structural and numerical chromosomal aberrations and abnormalities, as well as tests that evaluates induced DNA damages resulted from DNA strand breaks and DNA adducts.

Fig 1. An overview of types of DNA damage

In order to identify genotoxic chemicals early in the drug development process, Creative Bioarray has developed a variety of in vitro genotoxicity tests, including but not limited to:

•	Bacterial reverse mutation test OECD 471 Commonly known as Ames test, the bacterial reverse mutation test identifies chemicals that induce point mutations using Salmonella typhimurium and Escherichia coli that contain identified mutations in specific amino acid biosynthesis gene. Chemicals that can induce point mutations may induce a reverse mutation that enables the bacteria to grow on medium that lacks the required amino acid.
•	In vitro mammalian chromosomal aberration test OECD 473 The chromosomal aberration test is designed to identify chemicals that cause structural chromosomal aberrations using cultured mammalian peripheral blood lymphocytes or established mammalian cell lines, for example Chinese Hamster Ovary cell line (CHO). In this test, individual cells are examined under microscope for chromosomal aberrations following a short or long time exposure of test chemicals.
•	In vitro mammalian cell micronucleus test OECD 487 The in vitro micronucleus test, as chromosomal aberration test, can be conducted on cultured mammalian peripheral blood lymphocytes or established cell lines including CHO. It is used to identify chemicals that cause chromosomal breaks and aneuploidy.
•	In vitro gene mutation tests OECD 490 The gene mutation assays, using specific thymidine kinase (tk) heterozygous cell lines, are used to identify chemicals that cause gene mutations at the tk reporter locus. The chemical induced gene mutation can be evaluated by observing the size and appearing time of colonies and enumerating their frequencies.
•	In vitro comet assay In vitro comet assay, also known as single-cell gel electrophoresis (SCEG) assay, is a sensitive method to rapidly detect DNA damage in single cells, including double-strand breaks, single-strand breaks, and alkali labile sites.
•	Genotoxicity screening Creative Bioarray provides genotoxicity screening assays via Ames test, micronucleus test, and γH2AX detection.

Creative Bioarray, having gained deep knowledge and experience in toxicological research and compound safety evaluation throughout the years, is the first-choice partner for consulting and performing in vitro genotoxicity assays. We also provide in vitro toxicity assays on other tissues and organs. If you have any special needs or questions regarding our services, please feel free to contact us to get support from our experienced experts. We look forward to working with you in the near future.

References

Helleday, Thomas, Saeed Eshtad, and Serena Nik-Zainal. "Mechanisms underlying mutational signatures in human cancers." Nature Reviews Genetics 15.9 (2014): 585-598.
Žegura, Bojana, and Metka Filipič. Application of in vitro comet assay for genotoxicity testing. Humana Press, 2004.

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