Abstract 3581: Impact of Nrf2 on the development of ethyl carbamate/ butylated hydroxytoluene-induced lung tumorigenesis in mice.

Abstract

Abstract Chronic inflammation has been linked to the development of various types of cancers and has been recently recognized as the seventh hallmark of cancer. Accumulating evidence suggests that Nrf2 plays a pivotal role in protection against oxidative tissue damage and inflammation. Previous findings from ours as well as other laboratories have demonstrated that Nrf2 possesses the protection effects in the inflammation-associated carcinogenesis in preclinical models. The aim of the present study is to investigate the role of Nrf2 in butylated hydroxytoluene (BHT)-induced pulmonary inflammation and BHT-urethane/ethyl carbamate (EC) induced two-stage lung carcinogenesis. Nrf2 deficient mice showed an increased susceptibility to BHT-induced pulmonary inflammation, whereas Nrf2 WT mice have higher antioxidant proteins level and lower pro-inflammatory markers. Although lung inflammation was slightly more severe in Nrf2KO mice as compared to their wildtype counterpart, the tumor incidence and tumor multiplicity were found to be significantly lower in Nrf2KO mice treated with EC-BHT. Tumor multiplicity was also lower in Nrf2KO mice treated with EC alone. In summary, on one hand, Nrf2 is required to dampen inflammation, but Nrf2 may be disadvantage in EC or BHT-EC mediated lung tumorigenesis. Citation Format: Tien-Yuan Wu, Tin Oo Khor, Ka-Lung Cheung, Ah-Ng Kong. Impact of Nrf2 on the development of ethyl carbamate/ butylated hydroxytoluene-induced lung tumorigenesis in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3581. doi:10.1158/1538-7445.AM2013-3581