Abstract 3611: Benzo(a)pyrene exposure increases expression of HPV oncoproteins: a potential co-factor for increased cervical cancer among Northern Plains American Indian women.

Abstract

Abstract Introduction: Cervical cancer remains one of the most common and deadly cancers in women worldwide. There is a significant health disparity in the incidence and mortality of cervical cancer between American Indian and Caucasian women residing on the Northern Plains. The development of cervical cancer is closely associated with persistent infection with high risk HPV genotypes. Additionally, exposure to cigarette smoke is also a risk factor for cervical cancer. Our studies indicate that Northern Plains American Indian women have a high rate of both HPV infection and smoking. Our studies also show that American Indian women who tested positive for HPV were more likely to have an abnormal PAP test than HPV positive Caucasian women. While smoking is known to increase the risk of developing cervical cancer, the molecular interactions between HPV and smoke carcinogens are not well known. Herein, we determine the cellular and molecular effects of benzo-a-pyrene (BaP) (a carcinogen in cigarette smoke) on HPV oncoprotein expression in cervical cancer cells and elucidate the role of the aryl hydrocarbon receptor (AhR) in this process. Methods: The effects of BaP on HPV oncoproteins and AhR mediated molecular events was determined using cervical cancer cell line models and real time PCR, immunoblotting, immunostaining and flow cytometry analyses. The level of AhR activation in normal cervix and in cervical cancer tissues was also determined with immunohistochemical analysis. Results: Our results indicate that exposure to BaP, a tobacco carcinogen, activates the AhR pathway in a time and dose dependent manner, as determined by an increase in nuclear localization of AhR and increased expression of cytochrome p450 1A. Expsoure to BaP ultimately results in increased expression of HPV oncogenes. Importantly, curcumin, a natural compound, attenuated the BaP induced increase in the expression of HPV E7 oncoprotein. Interestingly, both cytoplasmic and nuclear localization of AhR is increased in cervical cancer tissue compared to normal cervical epithelium. Conclusion: Taken together this data imply that a high prevalence of HPV infection and a high exposure rate to BaP may synergize to increase the incidence and mortality of cervical cancer in American Indian women residing in the Northern Plains. We have identified curcumin as a potent compound that may be effective in attenuating oncogenic HPV infection. However, increased cervical cancer screening is warranted in addition to HPV vaccine and use of chemopreventive agents, such as curcumin, to effectively decrease the cervical cancer health disparity in Northern Plains American Indian women. Citation Format: Diane M. Maher, Maria Bell, Amanda Schaefer, Meena Jaggi, Subhash C. Chauhan. Benzo(a)pyrene exposure increases expression of HPV oncoproteins: a potential co-factor for increased cervical cancer among Northern Plains American Indian women. [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 3611. doi:10.1158/1538-7445.AM2013-3611