Characterization of the psychological, physiological and EEG profile of acute betel quid intoxication in naïve subjects

Betel quid use and abuse is wide spread in Asia but the physiological basis of intoxication and addiction are unknown. In subjects na?ve to the habit of betel quid intoxication, the psychological and physiological profile of intoxication has never been reported. We compared the effect of chewing gum or chewing betel quid, and subsequent betel quid intoxication, on psychological assessment, prospective time interval estimation, numerical and character digit span, computerized 2 choice tests and mental tasks such as reading and mathematics with concurrent monitoring of ECG, EEG and face temperature in healthy, non-sleep deprived, male subjects na?ve to the habit of chewing betel quid. Betel quid intoxication, dose dependently induced tachycardia (max 30 bpm) and elevated face temperature (0.7°C) (P<0.001) above the effects observed in response to chewing gum (max 12 bpm and 0.3°C) in 12 subjects. Gross behavioral indices of working memory such as numerical or character digit span in 8 subjects, or simple visual-motor performance such as reaction speed or accuracy in a two choice scenario in 8 subjects were not affected by betel quid intoxication. Betel quid intoxication strongly influenced the psychological aspects of perception such as slowing of the prospective perception of passage of a 1 minute time interval in 8 subjects (P<0.05) and perceived increased arousal (P<0.01) and perceived decreased ability to think (P<0.05) in 31 subjects. The EEG spectral profile recorded from mental states associated with open and closed eyes, and mental tasks such as reading and eyes closed mental arithmetic were significantly modified (P<0.05) relative to chewing gum by betel quid intoxication in 10 subjects. The prevalence of betel quid consumption across a range of social and work settings warrants greater investigation of this widespread but largely under researched drug.     

Characterization of the Psychological,Physiological and EEG Profile of Acute Betel Quid Intoxication in Na?ve Subjects

Betel quid use and abuse is wide spread in Asia but the physiological basis of intoxication and addiction are unknown. In subjects naïve to the habit of betel quid intoxication, the psychological and physiological profile of intoxication has never been reported. We compared the effect of chewing gum or chewing betel quid, and subsequent betel quid intoxication, on psychological assessment, prospective time interval estimation, numerical and character digit span, computerized 2 choice tests and mental tasks such as reading and mathematics with concurrent monitoring of ECG, EEG and face temperature in healthy, non-sleep deprived, male subjects naïve to the habit of chewing betel quid. Betel quid intoxication, dose dependently induced tachycardia (max 30 bpm) and elevated face temperature (0.7°C) (P<0.001) above the effects observed in response to chewing gum (max 12 bpm and 0.3°C) in 12 subjects. Gross behavioral indices of working memory such as numerical or character digit span in 8 subjects, or simple visual-motor performance such as reaction speed or accuracy in a two choice scenario in 8 subjects were not affected by betel quid intoxication. Betel quid intoxication strongly influenced the psychological aspects of perception such as slowing of the prospective perception of passage of a 1 minute time interval in 8 subjects (P<0.05) and perceived increased arousal (P<0.01) and perceived decreased ability to think (P<0.05) in 31 subjects. The EEG spectral profile recorded from mental states associated with open and closed eyes, and mental tasks such as reading and eyes closed mental arithmetic were significantly modified (P<0.05) relative to chewing gum by betel quid intoxication in 10 subjects. The prevalence of betel quid consumption across a range of social and work settings warrants greater investigation of this widespread but largely under researched drug.     

Accumulation of mitochondrial DNA deletions in human oral tissues -- effects of betel quid chewing and oral cancer

Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been associated with intrinsic aging and environmental insult. Recently, mtDNA mutations have been detected in various tumors, including head and neck tumors. However, the factors affecting the occurrence and accumulation of mtDNA deletions in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral tissues from the patients with or without betel quid chewing history. The results revealed that irrespective of the history of betel quid chewing, the incidences of the 4977bp deletion and other deletions of mtDNA were lower in the tumor portion as compared with the non-tumor portion. The average proportions of the 4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel quid chewers were 13- and 5-fold, respectively, lower than those in the corresponding non-tumor tissues. Moreover, the average proportion of 4977bp deleted mtDNA was significantly higher (P<0.05) in the non-tumor oral tissues of the patients with betel quid chewing history than that of the patients without the history of betel quid chewing. These results suggest that betel quid chewing may increase mtDNA mutation in human oral tissues and that accumulation of mtDNA deletions and subsequent cytoplasmic segregation of these mutations during cell division could be an important contributor to the early phase of oral carcinogenesis.     

Systematic Review and Meta-Analysis of Association of Smokeless Tobacco and of Betel Quid without Tobacco with Incidence of Oral Cancer in South Asia and the Pacific

Aim

This systematic review and meta-analysis aimed to critically appraised data from comparable studies leading to quantitative assessment of any independent association between use of oral smokeless tobacco in any form, of betel quid without tobacco and of areca nut with incidence of oral cancer in South Asia and the Pacific.

Methods

Studies (case control and/or cohort) were identified by searching Pub Med, CINAHL and Cochrane databases through June 2013 using the keywords oral cancer: chewing tobacco; smokeless tobacco; betel quid; betel quid without tobacco; areca nut; Asia, the Pacific and the reference lists of retrieved articles. A random effects model was used to compute adjusted summary OR_RE for the main effect of these habits along with their corresponding 95% confidence intervals. To quantify the impact of between-study heterogeneity on adjusted main-effect summary OR_RE, Higgins'' H and I₂ statistics along with their 95% uncertainty intervals were used. Funnel plots and Egger''s test were used to evaluate publication bias.

Results

Meta-analysis of fifteen case–control studies (4,553 cases; 8,632 controls) and four cohort studies (15,342) which met our inclusion criteria showed that chewing tobacco is significantly and independently associated with an increased risk of squamous-cell carcinoma of the oral cavity (adjusted main-effect summary for case- control studies OR_RE = 7.46; 95% CI = 5.86–9.50, P<0.001), (adjusted main-effect summary for cohort studies RR = 5.48; 95% CI = 2.56–11.71, P<0.001). Furthermore, meta-analysis of fifteen case control studies (4,648 cases; 7,847 controls) has shown betel quid without tobacco to have an independent positive association with oral cancer, with OR = 2.82 (95% CI = 2.35–3.40, P<0.001). This is presumably due to the carcinogenicity of areca nut. There was no significant publication bias.

Conclusion

There is convincing evidence that smokeless (aka chewing) tobacco, often used as a component of betel quid, and betel quid without tobacco, are both strong and independent risk factors for oral cancer in these populations. However, studies with better separation of the types of tobacco and the ways in which it is used, and studies with sufficient power to quantify dose-response relationships are still needed.     

Clastogenic effect for cigarette smoking but not areca quid chewing as measured by micronuclei in exfoliated buccal mucosal cells

The objective of this study was to use the micronuclei from exfoliated buccal mucosal cells to investigate the clastogenic effects of areca quid chewing and cigarette smoking, as well as the interaction between the two. The study population was selected from residents of seven villages recruited for a community-cohort study. A total of 141 subjects were recruited based on the regular consumption of cigarettes and betel quid. Salient personal characteristics were collected from interview using a specially designed questionnaire. Micronuclei were scored on Feulgen/fast green-stained smear preparations of exfoliated cells obtained by scraping the surface of the buccal mucosa. There was no significant interaction between the chewing of betel nut and cigarette smoking. Heavy smoking was positively associated with MN frequency, with areca quid chewing negatively associated. A significant positive trend was demonstrated for the relationship between MN frequency and either daily cigarette consumption or cumulative smoking pack-years. By contrast, negative trends were demonstrated for the analogous relationships with areca quid chewing. These results indicate that heavy smoking, but not areca quid chewing, increases MN formation. These findings suggest that the carcinogenesis of the oral cancers induced by areca quid chewing in Taiwan may be through a pathway other than genotoxicity.     

Chewing Betel Quid and the Risk of Metabolic Disease,Cardiovascular Disease,and All-Cause Mortality: A Meta-Analysis

Background

Betel nut (Areca nut) is the fruit of the Areca catechu tree. Approximately 700 million individuals regularly chew betel nut (or betel quid) worldwide and it is a known risk factor for oral cancer and esophageal cancer. We performed a meta-analysis to assess the influence of chewing betel quid on metabolic diseases, cardiovascular disease, and all-cause mortality.

Methodology/Principal Findings

We searched Medline, Cochrane Library, Web of Science, and Science Direct for pertinent articles (including the references) published between 1951 and 2013. The adjusted relative risk (RR) and 95% confidence interval were calculated using the random effect model. Sex was used as an independent category for comparison.

Results

Of 580 potentially relevant studies, 17 studies from Asia (5 cohort studies and 12 case-control studies) covering 388,134 subjects (range: 94 to 97,244) were selected. Seven studies (N = 121,585) showed significant dose-response relationships between betel quid consumption and the risk of events. According to pooled analysis, the adjusted RR of betel quid chewers vs. non-chewers was 1.47 (P<0.001) for obesity (N = 30,623), 1.51 (P = 0.01) for metabolic syndrome (N = 23,291), 1.47 (P<0.001) for diabetes (N = 51,412), 1.45 (P = 0.06) for hypertension (N = 89,051), 1.2 (P = 0.02) for cardiovascular disease (N = 201,488), and 1.21 (P = 0.02) for all-cause mortality (N = 179,582).

Conclusion/Significance

Betel quid chewing is associated with an increased risk of metabolic disease, cardiovascular disease, and all-cause mortality. Thus, in addition to preventing oral cancer, stopping betel quid use could be a valuable public health measure for metabolic diseases that are showing a rapid increase in South-East Asia and the Western Pacific.     

IL‐1β Promotes Malignant Transformation and Tumor Aggressiveness in Oral Cancer

Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin‐1 beta (IL‐1β) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro‐IL‐1β expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4‐Nitroquinolin‐1‐oxide (4‐NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro‐IL‐1β was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine‐derived nitrosamine ketone (NNK) and arecoline stimulated IL‐1β secretion in an inflammasome‐dependent manner. IL‐1β treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL‐6, IL‐8, and growth‐regulated oncogene‐α following IL‐1β stimulation. The conditioned medium of IL‐1β‐treated OSCC cells exerted significant proangiogenic effects. Crucially, IL‐1β increased the invasiveness of OSCC cells through the epithelial‐mesenchymal transition (EMT), characterized by downregulation of E‐cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL‐1β can be induced by tobacco and betel quid‐related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC. J. Cell. Physiol. 230: 875–884, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.     

Mutual interactions among ingredients of betel quid in inducing genotoxicity on Chinese hamster ovary cells

The purpose of this study is to explore the mutual interactions among the chemical ingredients of betel quid including arecoline, sodium fluoride, catechin and glycyrrhizin in producing genotoxicity on Chinese hamster ovary (CHO) cells using the micronucleus method. Our results show that arecoline at a rather low concentration of 0.2–2 μM which could be in the oral cavity during betel quid chewing and NaF (0.8–2.4 mM) significantly elevated the number of micronucleated cells in a concentration-dependent manner. In addition, significant prolongation of cell cycles was observed by treatment with arecoline (≥2.0 μM) or NaF (2.4 mM) in CHO cells. Both catechin and glycyrrhizin could antagonize not only the increased micronucleated cells induced by arecoline and NaF but also the prolonged cell cycle induced by arecoline in CHO cells. This finding implies that the adjuvant ingredients, catechu and liquorice root extract provide not only a flavor but also an antagonist against the genotoxicity of arecoline and fluoride containing betel quid.     

Evaluation of frequency of micronucleated oral mucosa cells as a marker for genotoxic damage in chewers of betel quid with or without tobacco.

The frequency of micronucleated cells (MNC) derived from exfoliated human oral mucosal cells has been measured to assess genotoxic damage in chewers of betel quid with tobacco (BQT) and tobacco with lime (T). Significantly elevated frequencies of MNC were observed in the exposed groups (BQT = 4.83 +/- 0.70; T = 5.20 +/- 0.66 per 1000 cells) compared to the control group (C = 2.59 +/- 0.37) although the levels observed were lower than those reported in the literature. No correlation was seen between age, duration and frequency of habits and the frequency of MNC in the 2 habit groups. Clastogenic agents in betel quid possibly involved in micronucleus formation are discussed.     

The Magnitude of Tobacco Smoking-Betel Quid Chewing-Alcohol Drinking Interaction Effect on Oral Cancer in South-East Asia. A Meta-Analysis of Observational Studies

Tobacco smoking, betel quid chewing and alcohol drinking are oral cancer risk factors. Observational studies unanimously report that oral cancer risk in smoking-drinking-chewing exposed subjects is exceptionally high. However, none of them assessed the fractions of this risk attributable to the three individual risk factors and to the smoking-drinking-chewing interaction. The present study sought to assess the magnitude of the smoking-drinking-chewing interaction effect on oral cancer. A meta-analysis of observational South-East Asian studies which reported oral cancer odds ratios (ORs) stratified for smoking-drinking-chewing exposures was performed. The pooled ORs were estimated and controlled for quality, heterogeneity, publication bias and inclusion criteria. The smoking-drinking-chewing interaction effect was estimated through the pooled Relative Excess Risk due to Interaction (RERI, excess risk in smoking-drinking-chewing exposed individuals with respect to the risk expected from the addition of the three individual risks of smoking, drinking and chewing). Fourteen studies were included with low between-study heterogeneity. The pooled ORs for smoking, drinking, chewing, smoking-drinking-chewing, respectively were 3.6 (95% confidence interval −95% CI, 1.9–7.0), 2.2 (95% CI, 1.6–3.0), 7.9 (95% CI, 6.7–9.3), 40.1 (95% CI, 35.1–45.8). The pooled RERI was 28.4 (95% CI, 22.9–33.7). Among smoking-drinking-chewing subjects, the individual effects accounted for 6.7% (smoking), 3.1% (drinking), 17.7% (chewing) of the risk, while the interaction effect accounted for the remaining 72.6%. These data suggest that 44,200 oral cancer cases in South-East Asia annually occur among smoking-drinking-chewing exposed subjects and 40,400 of these are exclusively associated with the interaction effect. Effective oral cancer control policies must consider concurrent tobacco smoking, alcohol drinking, betel quid chewing usages as a unique unhealthy lifestyle.     

Synergistic Effect of Betel Quid,Tobacco, and Alcohol in Cigarette Smoking Induced Micronuclei in a Population of Arunachal Pradesh,India

Genotoxicity is one of the important endpoints for risk assessment of various lifestyle factors. The present study examined the synergistic effect of tobacco, betel quid, and alcohol in cigarette smoking induced micronuclei (MN) in the buccal epithelia of exposed individuals. Analysis of MN frequency and nuclear abnormalities (binucleated, karyorrhectic, karyolitic, and pyknotic cells) was performed in the exfoliated buccal cells of 110 habituates and compared to a control group matched for gender, age, and habit. A significant increase in the frequency of MN was found in smokers and alcohol, betel quid, and tobacco users compared to the control group. Tobacco, alcohol, and betel quid seem to potentiate the effect of cigarette smoking induced MN formation in the buccal epithelium. Smoking alone significantly increased the number of karyorrhexis cells in the buccal epithelium and combined exposure of all four test substances significantly increased the number of karyorrhexis and pycnotic cells. The findings indicate a synergistic effect between smoking, betel quid, tobacco, and alcohol in MN induction and cell death in buccal cells of exposed individuals.     

A preliminary assessment of possible mutagenicity of betel nut and ingredients of the betel quid when administered alone or in combinations to larvae of Drosophila melanogaster.

The "carcinogenic" betel nut and constituents of betel quid were tested for possible mutagenicity in Drosophila. The test compounds were administered either alone or in combinations by larval feeding. The data on sex-chromosome loss, sex-linked recessive lethals and autosomal translocations suggest lack of mutagenicity.     

Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients

The formation of reactive oxygen species (ROS) from betel quid ingredients, namely areca nut, catechu and tobacco, was studied using a chemiluminescence (CL) technique. Aqueous extracts of areca nut and catechu were capable of generating superoxide anion and hydrogen peroxide at pH greater than 9.5. The formation of O2 was enhanced by Fe2+, Fe3+ and Cu2+ but inhibited by Mn2+. Tobacco extract failed to generate ROS under similar conditions. Saliva was found to inhibit both O2 and H2O2 formation from betel quid ingredients. Upon incubation of DNA at alkaline pH with areca nut extract and Fe3+ or catechu, 8-hydroxydeoxyguanosine was formed as quantified by high performance liquid chromatography (HPLC)/electrochemical detection. The data suggest a possible role of reactive oxygen species in the etiology of oral cancer in betel quid chewers.     

Investigation on the role of p53 codon 72 polymorphism and interactions with tobacco, betel quid, and alcohol in susceptibility to cancers in a high-risk population from North East India

The association of TP53 codon 72 polymorphism with cancer susceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally, and ethnically isolated population. The area reports high rate of tobacco usage in a variety of ways of consumption, compared with the rest of Indian population. A total of 411 cancer patients (161 lung, 134 gastric, and 116 oral) and 282 normal controls from the ethnic population were analyzed for p53 codon 72 polymorphism by polymerase chain reaction-restriction fragment length polymorphism. No significant difference in genotypic distribution of p53 between cases and controls was observed. Results suggested betel quid chewing as a major risk factor for all the three cancers (odds ratio [OR]=3.54, confidence interval [CI]=2.01-6.25, p<0.001; OR=1.74, CI=1.04-2.92, p=0.03; and OR=1.85, CI=1.02-3.33, p=0.04 for lung, gastric, and oral cancers, respectively). Tobacco smoking was associated with risk of lung and oral cancers (OR=1.88, CI=1.11-3.19, p=0.01 and OR=1.68, CI=1.00-2.81, p=0.04). Interactions between p53 genotypes and risk factors were analyzed to look for gene-environment interactions. Interaction of smoking and p53 genotype was significant only for oral cancer. Interactions of betel quid with p53 genotypes in lung cancer showed significant increase for all the three genotypes, indicating a major role of betel quid (OR=5.90, CI=1.67-20.81, p=0.006; OR=5.44, CI=1.67-17.75, p=0.005; and OR=5.84, CI=1.70-19.97, p=0.005 for Arg/Arg, Arg/Pro, and Pro/Pro, respectively). In conclusion, high incidence of these cancers in northeast India might be an outcome of risk habits; further, tissue- and carcinogen-specific risk modification by p53 gene is probable.     

Impact of VEGF-C Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan

Background

Oral cancer, which is the fourth most common male cancer, is associated with environmental carcinogens in Taiwan. Vascular endothelial growth factor (VEGF)-C, an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies. This study was designed to examine associations of five VEGF-C gene polymorphisms with the susceptibility to and clinicopathological characteristics of oral squamous cell carcinoma.

Methodology/Principal Findings

Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a real-time polymerase chain reaction (PCR) in 470 male patients with oral cancer and 426 cancer-free controls. In this study, we found that the VEGF-C rs7664413 and rs2046463 polymorphisms were associated with oral-cancer susceptibility but not with any clinicopathological parameters. The GGACA or GACTG haplotype of five VEGF-C SNPs (rs3775194, rs11947611, rs1485766, rs7664413, and rs2046463) combined was also related to the risk of oral cancer. Among 611 male smokers, VEGF-C polymorphism carriers who also chewed betel quid were found to have a 14.5–24.2-fold risk of having oral cancer compared to the VEGF-C wild-type carrier who did not chew betel quid. Among 461 male betel-quid chewers, VEGF-C polymorphism carriers who also smoked had a 2.7–18.1-fold risk of having oral cancer compared to those who carried the wild type but did not smoke.

Conclusions

Our results suggest that the two SNPs of VEGF-C (rs7664413 and rs2046463) and either of two haplotypes of five SNPs combined have potential predictive significance in oral carcinogenesis. Gene-environmental interactions among VEGF-C polymorphisms, smoking, and betel-quid chewing might alter one''s susceptibility to oral cancer.     

Mitochondrial DNA Copy Number and Risk of Oral Cancer: A Report from Northeast India

Background

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer globally. Tobacco consumption and HPV infection, both are the major risk factor for the development of oral cancer and causes mitochondrial dysfunction. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene–environment interactions and hence contributing to the individual susceptibility to cancer. Here, we have investigated the association of tobacco - betel quid chewing, HPV infection, GSTM1-GSTT1 null genotypes, and tumour stages with mitochondrial DNA (mtDNA) content variation in oral cancer patients.

Methodology/Principal Findings

The study comprised of 124 cases of OSCC and 140 control subjects to PCR based detection was done for high-risk HPV using a consensus primer and multiplex PCR was done for detection of GSTM1-GSTT1 polymorphism. A comparative ΔCt method was used for determination of mtDNA content. The risk of OSCC increased with the ceased mtDNA copy number (P_trend = 0.003). The association between mtDNA copy number and OSCC risk was evident among tobacco – betel quid chewers rather than tobacco – betel quid non chewers; the interaction between mtDNA copy number and tobacco – betel quid was significant (P = 0.0005). Significant difference was observed between GSTM1 - GSTT1 null genotypes (P = 0.04, P = 0.001 respectively) and HPV infection (P<0.001) with mtDNA content variation in cases and controls. Positive correlation was found with decrease in mtDNA content with the increase in tumour stages (P<0.001). We are reporting for the first time the association of HPV infection and GSTM1-GSTT1 null genotypes with mtDNA content in OSCC.

Conclusion

Our results indicate that the mtDNA content in tumour tissues changes with tumour stage and tobacco-betel quid chewing habits while low levels of mtDNA content suggests invasive thereby serving as a biomarker in detection of OSCC.     

Effect of chewing betel nut on measurements of salivary progesterone and estradiol

The measurement of steroids in saliva is both simple and non-invasive and has been widely used in field and clinical-based research. The observance of particular cultural practices by some populations, however, may hamper accurate hormonal analyses. The present study evaluated the effects of one such practice-the chewing of betel nut-on the accurate measurement of salivary progesterone and estradiol. A time series experiment was conducted among Bangladeshi women who are regular users of betel nut. Salivary steroids were analyzed by radioimmunoassay in samples collected prior to and then 30, 60, 120, and 240 min following betel quid use. Results show no significant difference between basal steroid levels and those obtained 60, 120, and 240 min after chewing betel nut. We conclude that with specific collection protocols that take into account time since chewing, salivary steroid analyses can be undertaken in populations among whom the practice of chewing betel nut is endemic.     

Oral implantology and oral carcinogenesis in primates

The projection of basic clinical research into practical application for the patient's benefit is one of the prime goals of biomedical research. The non-human primate, by its close proximity to man, affords an ideal experimental model to meet the needs of such scientific research. Our dentally orientated investigations have encompassed the fields of oral implantology and oral carcinogenesis. The former has delved into reimplantation of natural teeth and implantation of a variety of artificial substances such as: plastics, ceramics, and pyrolite carbons, which have been utilized for bone and/or tooth replacement in a variety of forms. The chemical carcinogenesis research effort has been directed toward identifying the carcinogenic substance in betel quid chewing, which is thought to be a major cause of the high incidence of oral cancer in India.     

The influence of pH on the convertogenic activity of plant phenolics

The genotoxicity of plant phenolics, including pyrogallol, gallic acid, resorcinol and catechin, and a water extract and tannin fraction of betel nut (Areca catechu) was examined at pH levels ranging from 5 to 10. Strain D7 of Saccharomyces cerevisiae was used since the cells can withstand a wide range of pH levels without any loss of viability. At alkaline pH ranges, the examined phenolics and betel nut extracts induced mitotic conversion, whereas they lacked this capacity at acid pH levels. This phenomenon may be due to the rapid autoxidation of phenolics under alkaline conditions, which leads to the generation of H2O2 and free radicals. The results indicate that plant phenolics may pose a genotoxic hazard during chewing of lime-containing betel quid and tobacco which causes the salivary pH to rise above 8.     

Betel Nut Chewing Is Strongly Associated With General and Central Obesity in Chinese Male Middle‐aged Adults

Betel nut chewing has been reported to increase the risk of cardiovascular disease and all‐cause mortality. The reason is unclear. In this study, we investigated the association between betel nut chewing and general obesity (BMI ≥25 kg/m²) and central obesity (waist circumference (WC) ≥90 cm). A total of 1,049 male subjects, aged ≥40 years, were recruited from Taichung city in Taiwan in 2004. The relationships between betel nut chewing and general and central obesity were studied by multiple linear and logistic regression analyses. The prevalence of current and former betel nut chewing was 7.0 and 10.5% in our male Taiwanese cohort. Current/former betel nut chewers had a higher prevalence of general and central obesity when compared with individuals who had never chewed betel nut. Adjusted for age, diabetes, hypertension, lipids, smoking, alcohol drinking, physical activity, income, and education level, the odds ratios (ORs; 95% confidence intervals) of general and central obesity among the lower consumption of betel nut chewers were 1.78 (1.07, 2.96) and 1.19 (0.70, 2.02), respectively, compared to 2.01 (1.18, 3.41) and 1.89 (1.10, 3.23), respectively, among higher consumption chewers compared to individuals who had never chewed betel nut. The increasing ORs of general and central obesity with higher betel nut consumption revealed dose–response effects. Using multiple linear regression analyses, after adjusting for potential confounders, betel nut consumption was statistically significantly associated with BMI and WC. In conclusion, betel nut chewing was independently associated with general and central obesity in Taiwanese men. Dose–response effects of the association between betel nut consumption and general obesity as well as central obesity were found.