Abstract B33: Dissecting the role of Nrf3 (NF-E2-related factor 3) in chemical carcinogenesis using knock-out mice
| Autor: | Zaynab Nouhi, Anna Derjuga, Marilène Paquet, Grégory Chevillard, Volker Blank |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Cancer Research. 69:B33-B33 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | In this study, we investigated the role of the transcription factor Nrf3 in chemical carcinogenesis induced by benzo[a]pyrene, a common carcinogen found in cigarette smoke, car exhaust and charcoal-grilled meats. Wild type and Nrf3-deficient mice were treated weekly for 4 consecutive weeks with benzo[a]pyrene and then sacrificed 30 weeks after the first administration of carcinogen. Here, we report that mice exposed to benzo[a]pyrene rapidly exhibit labored breathing further accompanied with different signs of morbidity. Kaplan-Meyer survival rate analyses indicate that mice deficient for Nrf3 die earlier that wild type mice following benzo[a]pyrene exposure. Upon necropsy, gross morphology analyses showed the presence of an increased number of lung and thymus lesions in Nrf3-deficient mice compared to wild type mice whereas the number of stomach lesions is identical in both genotypes. Pathology analysis strongly suggests that observed lesions in lung and thymus are from lymphoma origin. Overall, our study reveals that mice deficient for Nrf3 are highly sensitive to chemicalinduced carcinogenesis suggesting a protective role of the transcription factor Nrf3 in this process. This provides new important insights into the molecular mechanisms involved in the development of lymphomas induced by chemical agents. We also propose the Nrf3-deficient mice as a new in vivo model to study tumor formation and response to chemoprotective agents. Citation Information: Cancer Res 2009;69(23 Suppl):B33. |
| Databáze: | OpenAIRE |
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