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

摘要: TP53 is one of the most commonly mutated genes in human tumours. Variations types and frequencies mutations at different tumour sites suggest that they may provide clues to identity causative mutagenic agent. A useful model for studying mutagenesis partial knock-in (Hupki) mouse containing exons 4-9 place corresponding exons. For an vitro assay, embryo fibroblasts from Hupki can be examined generation selection because cells immortalized by mutation Tp53 alone. Thus far, four environmental carcinogens have been using fibroblast immortalization assay: (a) UV light, which linked skin cancer; (b) benzo[a]pyrene, associated with tobacco smoke-induced lung (c) 3-nitrobenzanthrone, a suspected carcinogen diesel exposure; (d) aristolochic acid, Balkan endemic nephropathy-associated urothelial cancer. In each case, unique pattern was generated corresponded found tumours where exposure these agents has documented. Therefore, assay sufficient specificity make it applicable other mutagens putatively play role cancer aetiology. Despite utility current several limitations could addressed future developments, order improve its sensitivity selectivity.