Background Areca nut (AN) chewing is carcinogenic and biomarkers reflecting it are urgently needed to determine the effectiveness of emergent cessation programs. Buccal cells (BCs) may serve as an ideal matrix to measure such biomarkers; however, their utility for this purpose is unknown. Direct analysis in real time−mass spectrometry (DART−MS) is a sensitive technique that analyzes materials in the open air and requires minimal/no sample preparation. We utilized DART−MS to analyze BCs to test the usefulness of this method in measuring areca alkaloids as biomarkers for AN chewing. Methods We applied DART−MS in positive‐ion mode to quantitate over time human BCs: (a) exposed ex vivo to betel quid extracts (BQE) consisting of young AN, Piper betle L. leaf, slaked lime, and tobacco; and (b) obtained from seven chewers before and after BQ chewing. Quantification was performed by normalizing DART−MS alkaloid signal intensities to cholesterol intensities. Results Signals for areca alkaloids arecoline and arecaidine‐guvacoline were detected in BCs exposed ex vivo to BQE up to 7 days (the last day tested) after exposure and in BCs from chewers up to 3 days (the last day tested) post chewing. Discussion The presence of alkaloid signals in BQ‐exposed BCs verified BCs as a valid matrix and DART−MS as a suitable technique to measure biomarkers for AN chewing and provided reliable information on AN chewing timing. Conclusion DART−MS analyses of BCs can be used to accurately determine areca alkaloids as AN chewing biomarkers up to 3 days post chewing and possibly longer.
Areca (betel) nut chewing is the 4th most used psychoactive substance in the world and is chewed by approximately 600 million people in the world. In Monograph 85 (2004), the International Agency for Research on Cancer deemed betel nut chewing with and without tobacco an oral carcinogen. In 2006, the NCI-sponsored University of Guam/University of Hawaii Cancer Center Partnership to Advance Cancer Health Equity began to identify areas in the monograph where research efforts were needed, and thus initiated betel nut research in the Western Pacific. Some countries in this region have reported rates of oral cancer mortality as high as 80% compared to the average worldwide 5-year cumulative of less than 50%. Over the past 12 years, a research framework to study betel nut exposure and oral cancer outcomes has evolved within the partnership. To date, 11 betel nut studies have been funded by this partnership: three molecular studies, three population measures studies, three mechanistic studies, and two prevention studies, including an intervention trial. Of the 11 studies, the majority of the research is focused on the measurement of betel nut exposure and carcinogenicity (55%), followed by the measurement of pathological changes (27%) and the prevention of oral cancer (18%). The partnership's investment has resulted in numerous community collaborations, 18 peer-reviewed publications (13 in population sciences and 5 in basic sciences), and contributions to policy prohibiting the sale of betel nut to minors. Betel nut research faculty are also involved in other federally funded research studies with a betel nut component in the Western Pacific region. The partnership's Betel Nut Research Group will continue to strengthen its research infrastructure, contribute to the scientific literature related to betel nut chewing, expand the research to other health outcomes, and translate the findings into appropriate practices, programs, and policies to control and prevent betel nut-associated cancer and other health outcomes in Pacific Island communities. Citation Format: Yvette C. Paulino, Laura Biggs, Wayne Buente, Francis S. Dalisay, Christine E. Farrar, Adrian Franke, Brenda Y. Hernandez, Ana Joy Mendez, Reinhold Penner, Pallav Pokhrel, Hali Robinett, Jian Yang, Thaddeus A. Herzog. University of Guam/University of Hawaii Cancer Center Partnership leads areca (betel) nut research in the Pacific Islands [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A116.
Background: Betel nut is used by an estimated 600 million people globally and is the 4th most widely used psychoactive substance in the world. Its use has been shown to cause oral and esophageal cancers. Therefore, cessation programs are needed in which an effective biomarker can be employed.Objectives: Buccal cells are highly exposed to the betel nut during its use and are also easy to collect. However, it is unknown if there are significant changes to these cells upon exposure or how long any changes may last as the turnover of buccal cells is relatively fast. We sought to determine if optical changes could be detected on buccal cells after exposure to betel nut and if detected, how long these changes were sustained.Methods: Flow cytometry was employed to determine whether fluorescence intensities differ between buccal cells exposed to betel nut and naïve cells. We further characterized the optical signature of buccal cells exposed to betel nut and other polyphenol-rich substances using lambda scans performed on a laser scanning confocal microscope. Results:We demonstrate that the fluorescence of betel nut exposed cells is greater than that of cells exposed to other optically active compounds such as polyphenol-rich foods. We also demonstrate that the fluorescence spectra of betel nut quid exposed cells is distinct from that of cells exposed to other polyphenol-rich substances. Conclusions:We conclude that detecting the altered fluorescence of buccal cells following exposure to betel nut quid may serve as a candidate biomarker for betel nut quid use.
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