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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer.

Authors: Khor, Tin Oo; Huang, Mou-Tuan; Prawan, Auemduan; Liu, Yue; Hao, Xingpei; Yu, Siwang; Cheung, William Ka Lung; Chan, Jefferson Y; Reddy, Bandaru S; Yang, Chung S; Kong, Ah-Ng

Published In Cancer Prev Res (Phila), (2008 Aug)

Abstract: The nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting various tissues against inflammation, which is a potential risk factor for colorectal and other cancers. Our previously published mouse model work showed that Nrf2 helps protect against dextran sulfate sodium (DSS)-induced colitis/inflammation, and others have shown that Nrf2 helps protect against inflammation-associated colorectal carcinogenesis (aberrant crypt foci). The present study extended these important earlier findings by exploring the role of Nrf2 in colitis-associated colorectal cancer in a mouse model involving azoxymethane/DSS-induced colorectal carcinogenesis in Nrf2 knockout mice. Azoxymethane/DSS-treated Nrf2 knockout mice had increased incidence, multiplicity, and size of all colorectal tumors, including adenomas, versus treated wild-type (WT) mice, and the proportion of tumors that were adenocarcinoma was much higher in knockout (80%) versus WT (29%) mice. Compared with WT mice, knockout mice also had increased markers of inflammation in tumor tissue (cyclooxygenase-2 and 5-lipoxygenase expressions and prostaglandin E(2) and leukotriene B(4) levels) and in inflamed colonic mucosa (nitrotyrosine expression), supporting the association of knockout mouse tumor formation with inflammation. The phase II detoxifying/antioxidant enzymes NAD(P)H-quinone reductase 1 and UDP-glucurosyltransferase 1A1 were elevated in the normal mucosa of WT, but not Nrf 2 knockout, mice treated with azoxymethane/DSS. Our findings show that Nrf2 plays a critical role in protecting against inflammation-associated colorectal cancer.

PubMed ID: 19138955 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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