Linking environmental carcinogen exposure to TP53 mutations in human tumours using the human TP53 knock-in (Hupki) mouse model

Linking Environmental Carcinogen Exposure to TP53 Mutations in Human Tumours Using the Human TP53 Knock-in (Hupki) Mouse Model

Tác giả: Jill E. Kucab, David H. Phillips and Volker M. Arlt

Lĩnh vực: Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK

Nội dung tài liệu:
This review article discusses the critical role of the TP53 gene in human cancers and explores the utility of the human TP53 knock-in (Hupki) mouse model for investigating the link between environmental carcinogen exposure and TP53 mutations. The Hupki model, which incorporates human TP53 exons into the mouse genome, allows for the study of TP53 mutagenesis in embryo fibroblasts. The article details how this model has been used to examine the mutation patterns induced by four environmental carcinogens: UV light, benzo[a]pyrene, 3-nitrobenzanthrone, and aristolochic acid. The findings suggest that each carcinogen generates a unique TP53 mutation signature, mirroring patterns observed in human tumors, thereby highlighting the specificity of the Hupki embryo fibroblast immortalization assay. While acknowledging the assay’s utility, the authors also identify limitations and propose future modifications to enhance its sensitivity and selectivity for a broader application in cancer etiology research.

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