People diagnosed with malignant neoplasms often feel afraid and alone. However, cancer is largely an avoidable disease, and studies have shown that more than two-thirds of cancer deaths may be prevented through lifestyle modification, early detection and effective treatment. The World Health Organization (WHO) estimates that nearly 12.7 million new cases and 7.6 million cancer deaths occurred worldwide in 2008 (27). Oral cancers are malignant neoplasms that affect the structures or tissues of the mouth. They may be a primary lesion that originated in the mouth, a metastasis from a distant site, or an extension from an adjoining site. In quoting detailed epidemiological data, it is necessary to distinguish between these origins, and to ascertain which structures are included, e.g. the vermillion borders of the lips are sometimes included and sometimes not. Globally, 'oral cancer' is the eighth most common cause of cancer-related deaths, although many people are unaware of its existence (92). Of these oral cancers, more than 90% are squamous cell carcinomas arising in the mucous membranes of the mouth and oro-pharynx.

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Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiology and aetiology.

Habitual chewing of "betel nut" preparations constitutes the fourth most common human self-administration of a psychoactive substance after alcohol, caffeine, and nicotine. The primary active ingredient in these preparations is arecoline, which comes from the areca nut, the key component of all such preparations. Arecoline is known to be a relatively non-selective muscarinic partial agonist, accounting for many of the overt peripheral and central nervous system effects, but not likely to account for the addictive properties of the drug. We report that arecoline has activity on select nicotinic acetylcholine receptor (nAChR) subtypes, including the two classes of nAChR most related to the addictive properties of nicotine: receptors containing α4 and β2 subunits and those which also contain α6 and β3 subunits. Arecoline is a partial agonist with about 6-10% efficacy for the α4* and α6* receptors expressed in Xenopus oocytes. Additionally, arecoline is a silent agonist of α7 nAChR; while it does not activate α7 receptors when applied alone, it produces substantial activation when co-applied with the positive allosteric modulator PNU-120696. Some α7 silent agonists are effective inhibitors of inflammation, which might account for anti-inflammatory effects of arecoline. Arecoline's activity on nAChR associated with addiction may account for the habitual use of areca nut preparations in spite of the well-documented risk to personal health associated with oral diseases and cancer. The common link between betel and tobacco suggests that partial agonist therapies with cytisine or the related compound varenicline may also be used to aid betel cessation attempts.

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Nicotinic Activity of Arecoline, the Psychoactive Element of "Betel Nuts", Suggests a Basis for Habitual Use and Anti-Inflammatory Activity

Smokeless tobacco and areca nut usage are integral cultural traditions in South Asia. Paan and gutka are two commonly used products which contain these ingredients. They are immensely popular in South Asia and with South Asian immigrants. Regular paan and gutka use is associated with several deleterious health consequences, most significantly oral cancer. Of particular concern is the markedly increased risk of oral cancer in South Asian immigrants when compared with the natives in new areas of settlement. The South Asian community in the United States is large and rapidly growing. Paan and gutka are legal in the United States, and readily available in ethnic enclaves. Smokeless tobacco prevention and cessation research and interventions have not yet addressed the unique sociocultural circumstances of this growing, at-risk community. The medical, dental, and public health communities need to join forces to combat this emerging threat.

Paan and Gutka in the United States: An Emerging Threat

Betel nut chewing during pregnancy, Madang province, Papua New Guinea.

In most parts of the world, tobacco is used for smoking, whereas, in India, tobacco is used for smoking as well as in diverse smokeless forms. Absorption of toxic and carcinogenic chemicals in tobacco and other ingredients added to various products are causally associated with several non-communicable diseases including cancer, especially oral cancer, which is the leading cancer among men and the third most common cancer among women in India. This article highlights the toxicity, mutagenecity and carcinogenic effects of hazardous chemicals present in smokeless tobacco products. This endeavor was based on the extensive review of literature from various sources. The SLT products have influence on cellular metabolism, ability to cause DNA damage, and cancer in experimental animals. It is, therefore, essential to consider the collective role of chemical constituents of SLT products in the causation of adverse effect on human health.

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Chemistry and toxicology of smokeless tobacco

A capillary zone electrophoretic (CZE) method for the rapid analysis of the major alkaloids (arecoline and guavacoline) in areca nut extract is described. Areca nuts were pulverized and then extracted with water by sonication in a water bath. After centrifugation, the supernatant was analysed on a fused-silica capillary with 100 mM ammonium acetate-acetic acid (pH 4.6) as the running buffer at a voltage of 20 kV and temperature of 30 degrees C. The method is applicable to the analysis of alkaloids in the nut, commercial preparations (pan masala) and in the saliva of areca nut chewers.

C K Lim

Papers

Chemical and analytical aspects of areca nut.