The Big Blue Mouse Transgenic Rodent Mutation (TRM) assay has been recommended for the assessment of potential mutagenicity by the Organization for Economic Co-Operation and Development (OECD) for many years as part of test guideline 488.
The OECD - a multicountry organisation intended to promote economic development - adopted the latest version of 488 in July just months after Bioreliance acquired exclusive rights to the Big Blue Mouse assay from Agilent, which prompted the SAFC unit to reassess the test according to Robert Young, study director for TRM Assays.
He told BioPharma-Reporter.com that: “In 1991, BioReliance [then Microbiological Associates] received a contract to make a purpose built transgenic rodent to validate mutagenicity.
“When BioReliance gained exclusive rights to the assay and colonies this March, the main focus was on re-qualifying the service and bringing it up to speed with new guidelines line by line.”
Young explained that this work had involved updating the dosing and sampling time frames to expand the assay to measure mutations in the germ cell, which has previously not been performed.
“This means that we can now measure DNA damage in germ cells early on, or we can choose to wait a longer period of time to apply the assay. This has enhanced the assay with a reproducible and functional assay that gives homogeneous data for groups – that was a large part of our effort in the qualification stages.”
The ability to test for damage at the DNA levels is unique to the Big Blue Mouse assay according to Scott Hickman, marketing Manager for Bioreliance’s toxicology testing business.
“Big Blue is designed as a follow up assay that can be applied to any type of pharmaceutical, industrial consumer chemical, or cosmetic, which appears to have mutagenic properties. In other words, the method can be applied to any product that has the capability of causing DNA damage in humans.”
He added that: “It is important to note that Big Blue is a tier 2 assay. This type of assay is typically utilized after the tier 1 assays have been completed. Tier 1 assays also test for a compound’s ability to cause genetic damage, but are mostly carried out as in vitro studies.
“Big Blue is the only transgenic rodent mutation (TRM) assay that can go deeper and test for mutagenicity (mutations such as cancer) at the DNA level, as well as determining the types of DNA damage caused.”