Although in-vitro bacterial mutation assays and murine models have long been the gold standard for identifying DNA reactive genotoxic chemicals, the Ames Test method (as this is widely known) has significant limitations, which is why many researchers are now turning to transgenic rat models for toxicological studies. This is because the rat model offers numerous advantages over its mouse counterparts:
- Rats live longer than mice and have the ability to display a wider range of human-like tumors
- Rats have a larger body mass than mice, meaning researchers can more easily harvest samples from organs to study, among other things, pharamacokinetics and toxicokinetics.
- Rats have more similar carcinogenic reactions to humans. For example, aflatoxin B1 and tamoxifen both are known to cause cancer in humans (and rats) but show negative mutagenic/carcinogenic responses in mice.
Moreover, recent advances in gene editing technologies, including CRISPR/Cas9 has made significant waves in the field of biomedical research, including the study of mutagenesis and carcinogenesis. As a result, creating transgenic rats has become significantly easier, which will allow for increasingly greater numbers of rat models for the study of human-like carcinogenic responses.
According to a recent peer review of papers dealing with transgenic rat models for the study of mutagenesis and carcinogenesis, Nohmi, et al conclude that based on the literature they reviewed these rat models are “useful tools for various purposes such as regulation of chemicals, chemoprevention studies and mechanistic investigations.” Furthermore, this paper asserts that “advanced sequencing technology coupled with transgenic rat models may contribute significantly to further development of research on chemical mutagenesis and carcinogenesis.”
Thanks to the availability of more sophisticated transgenic rat models, the ability for researchers to more accurately predict toxicological reactions in humans in a preclinical setting is rapidly increasing.