The influence of TP53 status on the metabolic activation of environmental carcinogens
Final Report Abstract
Overall our data in vitro and in vivo suggest that specific XMEs and thus the activation of several environmental compounds are influenced by p53. We could show in vitro that p53 binds to the p53 responsive element of Cyp1a1 upon BaP treatment, thus enhancing BaP activation and DNA adduct formation. The influence of p53 on carcinogenic metabolism and DNA damage was confirmed in vivo. Alterations of DNA adduct formation depending on p53 status were observed for BaP or PhIP, both of them usually being metabolized by either Cyp1a1/2 or Sult1a1. No changes in DNA damage according to p53 status were observed for the carcinogens AAI or 3-NBA that are mainly activated by Nqo1. These results suggest that Cyp1a1 and Sult1a1, but not Nqo1 is regulated by p53, adding another important role to the functions of the tumor suppressor p53.
Publications
- Comparison of the metabolic activation of environmental carcinogens in mouse embryonic stem cells and mouse embryonic fibroblasts. Toxicology in Vitro, Volume 29, Issue 1, February 2015, Pages 34-43
Krais, A. M.; Mühlbauer, K.; Kucab, J. E.; Chinbuah, H.; Cornelius, M. G.; Wei, Q.-X., Phillips, D. H.; Hollstein, M.; Arlt, V. M.; Schmeiser, H.
(See online at https://doi.org/10.1016/j.tiv.2014.09.004)
