In Vivo Pig-a Gene Mutation Assay
The Pig-a gene mutation assay (OECD 470) is a genetic toxicology assay used for measuring mutations caused by effects of exposure to drugs or chemicals. The Pig-a assay is a follow-up assay to a positive in vitro mutation assay, such as the Ames or mammalian mutation assay. Gene mutation assays, like the Pig-a assay, measure the induction of mutations at a specific gene location, the phosphatidylinositol glycan class A gene (Pig-a), as opposed to measuring overall DNA damage.
Because Pig-a mutations tend to accumulate with repeated exposure to mutagens, and the mutated erythrocytes remain for a prolonged time in peripheral blood, the assay typically uses 28 days of repeat dosing. This allows for mutant accumulation and expression and allows for the potential to integrate into an ongoing repeat dose toxicity study.
At Inotiv, the Pig-a assay is typically run in rats.
Clear advantages of the Pig-a Assay include:
- Easily integrates into standard repeat dose toxicity studies
- Reduces animal use
- Use of standard laboratory rodents alleviates the need for expensive transgenic rodent mutation assays
- Fast, quantifiable results with flow cytometry
The entire Pig-a assay can be performed at Inotiv, or blood samples collected at another lab can be sent to Inotiv for analysis. The assay can be performed alone or in conjunction with other endpoints (Micronucleus Assay, Comet Assay, etc.).
Pig-a Assay Frequently Asked Questions (FAQs):
When is Pig-a required to be run?
The Pig-a assay is used as a follow-up to a positive Ames or in vitro gene mutation test. It can be used when metabolic activation was not required for the in vitro positive response if the test material is bioavailable to the bone marrow compartment.
Which species is preferred for Pig-a?
The Pig-a assay can be performed in rats or mice, although rats are more frequently used.
Is Pig-a run in both sexes or one?
Typically, one sex is sufficient. When data demonstrate relevant differences for the test chemical between males and females (e.g., differences in systemic toxicity, metabolism, and bioavailability), evaluation of both sexes is recommended.
How long does it take to run a Pig-a assay?
Typically, a 7-day (or longer) dose range finder test is first performed to select doses for the definitive study which is conducted for 28 days.
Explore other genetic toxicology assays:
| Mutation | Cytogenetic Damage | DNA Damage |
|---|---|---|
| Ames assay | In Vitro Micronucleus assay | Comet assay |
| HPRT assay | Chromosome Aberration assay | |
| Mouse Lymphoma assay | In Vivo Micronucleus assay | |
| Pig-a assay |
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