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PubMed1991

Cytogenetic surveillance of tobacco-areca nut (mava) chewers, including patients with oral cancers and premalignant conditions.

Three cytogenetic endpoints were studied in non-chewing healthy controls and 3 groups of tobacco-areca nut chewers, viz. normal chewers, chewers with oral submucous fibrosis and chewers with oral cancer. Frequencies of sister-chromatid exchanges and chromosome aberrations in peripheral blood lymphocytes and of micronucleated cells in exfoliated buccal mucosa were evaluated. All the parameters showed statistically significant elevations in all 3 groups of chewers compared to the controls. The data indicate possible application of the parameters as sensitive endpoints for monitoring tobacco-areca nut chewers, the group of individuals at higher risk of developing oral cancer, the commonest cancer among Indian males.

Adolescent↗
PubMed1989

Identification in rats of N-nitrosonipecotic acid as a major urinary metabolite of the areca-nut alkaloid-derived nitrosamines, N-nitrosoguvacoline and N-nitrosoguvacine.

N-Nitrosamines derived from areca-nut alkaloids have been implicated in cancer of the oral cavity and esophagus caused by betel quid chewing in India and other Asian countries. A major urinary metabolite of N-nitrosoguvacoline and N-nitrosoguvacine, both present in saliva of betel quid chewers of ppb levels, was isolated from rat urine and identified as N-nitrosonipecotic acid by comparison with the authentic compound. When a dose of 50 or 500 micrograms/rat of either compound was administered orally to BDIV rats, 66-85% of the dose was excreted in the urine as N-nitrosonipecotic acid and 2-8% as N-nitrosoguvacine. These N-nitrosamino acids could be analysed in the urine of betel quid chewers as a marker of exposure to areca-nut specific nitrosamines.

Animals↗
PubMed2006

Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers.

Areca (betel)-chewing is tightly associated with the high prevalence of oral squamous cell carcinoma (OSCC) in Asians. NFKB1 encodes a 105kDa protein that can be processed to produce p50 subunit of nuclear factor-kappaB protein complex. A insertion (ins)/deletion (del) polymorphism (-94ins/delATTG) in NFKB1 promoter, which may drive the ins allele two-fold increase in NFKB1 transcription relative to del allele, was recently found. This study identified that the odds ratio in OSCC carrying ins allelotype were 1.78 relative to controls (56.7 vs 41.8%) in subjects more than 50 years old. L allelotype of Heme oxygenase-1 (HO-1), accounting for a long (GT)(n) repeat in HO-1 promoter, is associated with the risks of areca-related OSCC. Subjects carried both NFKB1 ins and HO-1 L allelotypes had significant risks for various subsets of OSCC. OSCC with lymph node metastasis or advanced stage had significantly higher frequency of NFKB1 ins and HO-1 L allelotypes. This study suggested that the functional NFKB1promoter polymorphism could be valuable for assessment of cancer risk.

Adult↗
PubMed2006

Comparison of treatment potential of electrocoagulation of distillery effluent with and without activated Areca catechu nut carbon.

Physico-chemical characteristics of distillery effluent samples have been determined. The water quality parameters (WQPs) measured are colour, pH, electrical conductivity, turbidity, total dissolved solids (TDS), chloride, total hardness (THA), calcium, iron, bio-chemical oxygen demand (BOD) and chemical oxygen demand (COD). Almost all the values of WQPs of the distillery effluents have been found to be very high and well above the permissible limit suggested by Bureau of Indian Standards (BIS). Electrocoagulation (EC) technique is employed to treat the distillery effluents. Removal efficiency of WQPs is compared by adopting EC technique with and without the addition of indigenously prepared activated areca nut [botanical name: Areca catechu; kotta pakku, in (vernacular)] carbon (AAC). About 99% of turbidity has been removed in both the cases. The experimental results also revealed that the WQPs like EC, TDS, etc. of the effluents could be reduced. Loss of weight of sacrificial electrode (anode) is also ascertained. EC with AAC is found to be more effective than EC without AAC.

Aluminum↗
PubMed2004

Safrole-DNA adducts in human peripheral blood--an association with areca quid chewing and CYP2E1 polymorphisms.

It has been recently demonstrated that safrole (4-allyl-1,2-methylenedioxybenzene)-DNA adducts are present in oral cancer tissue from patients who have chewed areca quid (AQ) containing high concentration of safrole. In this study, the presence of safrole-DNA adducts in peripheral white blood cells from 88 subjects with a known AQ chewing history and 161 matched controls were studied with the aim of identifying the adducts as a biomarker for safrole exposure. This study also analyzed the correlation between the level of safrole-DNA adducts and polymorphism of the CYP2E1 gene, alone and in combination with the GST M1 and GST T1-deletion polymorphisms. The results demonstrated the presence of safrole-DNA adducts in 83 (94.32%) of the DNA samples from subjects with current AQ chewing history and 21 (13.04%) of the control samples without known AQ chewing habit ( [Formula: see text] ). Individuals with at least one CYP2E1 c2 allele had a significant higher frequency of safrole-DNA adducts (odds ratio (OR), 4.00; 95% confidence interval (CI), 1.03-15.53) than those with the CYP2E1 c1c1 genotype while chewing less than 20 areca quids per day. In conclusion, this study demonstrates the presence of safrole-DNA adducts in peripheral blood lymphocytes (PBL), and the presence of these safrole-DNA adducts is correlated with AQ chewing. In addition, the CYP2E1 would seem to play an important role in the modulation of safrole-DNA adduct formation.

Adult↗
PubMed2000

Behavioral and biochemical studies of dichloromethane fraction from the Areca catechu nut.

The dichloromethane fraction from Areca catechu was found to inhibit monoamine oxidase type A isolated from the rat brain with an IC50 of 665 +/- 65.1 microg/ml. Studies with pharmacological models of depression, i.e., forced swim and tail-suspension tests, indicated that it caused significant reduction in the immobility time similar to that of moclobemide (a selective inhibitor of MAO-A) without causing a significant change in motor performance. Alkaloids such as arecaidine, arecoline, and a few other constituents, reported to be present in Areca catechu were also tested, but none of them were found to inhibit MAO. Present study suggests that the dichloromethane fraction from A. catechu possesses antidepressant property via MAO-A inhibition.

Animals↗
PubMed2006

Prognostic role of c-Jun activation in patients with areca quid chewing-related oral squamous cell carcinomas in Taiwan.

BACKGROUND: Overexpression or activation of c-Jun has been implicated in the pathogenesis of several types of cancer. Treatment of oral cells with areca nut extract in culture can increase c-Jun proto-oncogene mRNA levels. The purpose of this study was to investigate the possible role of c-Jun activation in the pathogenesis and prognosis of areca quid chewing-related oral cancer in Taiwan. METHODS: We immunohistochemically examined c-Jun protein activation in human oral squamous cell carcinomas (SCC) using an anti-phosphospecific c-Jun (pc-Jun) antibody on paraffin-embedded sections. RESULTS: Positive pc-Jun staining was observed in 42 of 70 (60%) cases of oral SCC. No significant correlation was found between pc-Jun expression and patients' age, gender, oral habit, cancer location, clinical stage, tumor size and lymph node status. Kaplan-Meier curves showed that oral SCC patients with positive pc-Jun staining or positive lymph node metastasis had significantly shorter overall survival (p < 0.018 and 0.001, respectively, by log-rank test). CONCLUSION: These results indicate that c-Jun activation may play an important role in the carcinogenesis of oral SCC. Positive pc-Jun staining may serve as an adjuvant marker of worse prognosis in patients with oral SCC in Taiwan.

Areca↗
PubMed2000

Induction of the c-jun protooncogene expression by areca nut extract and arecoline on oral mucosal fibroblasts.

To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in human oral mucosal fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increase was transient and the level of c-jun mRNAs returned rapidly to control levels thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at detectable levels. During AQ chewing, oral mucosal cells are continuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a minimal effect on arecoline-induced c-jun expression. Therefore, arecoline-induced c-jun expression is independent of GSH depletion.

Areca↗
PubMed2002

Mutations of the adenomatous polyposis coli gene in areca quid and tobacco-associated oral squamous cell carcinomas in Taiwan.

BACKGROUND: Adenomatous polyposis coli (APC) gene mutations have been demonstrated not only in colorectal tumors but also in a variety of human cancers. METHODS: To elucidate the possible roles of APC gene mutations in oral squamous cell carcinomas (OSCCs), we examined 40 untreated human primary OSCCs using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing assays. RESULTS: By screening nearly one-half of the coding region (codons 279-1673, including the MCR) of the APC gene, five missense mutations and a 1-base pair deletion were detected in five (12.5%) tumors, resulting in five amino-acid substitutions or a truncation of the APC protein. All patients with APC mutations were both areca quid chewers and tobacco smokers (P = 0.049). CONCLUSIONS: These results suggest that APC mutations may also contribute to the carcinogenesis of at least some OSCCs in Taiwan, especially for the users of areca quid and tobacco.

Adenomatous Polyposis Coli Protein↗
PubMed2003

Areca nut extract treatment elicits the fibroblastoid morphological changes, actin re-organization and signaling activation in oral keratinocytes.

BACKGROUND: Areca (named as betel) is an important etiological factor linked with the high prevalence of oral squamous cell carcinoma (OSCC) in South-Asian countries. This in vitro study investigated the cellular changes and signaling activation in oral keratinocytes in response to areca nut extract (ANE) treatment. METHODS: Normal human oral keratinocyte (NHOK) and oral epidermoid carcinoma cell, Meng-1 (OECM-1) OSCC cell line were treated with variable dosages of ripen ANE. The morphological and cytoskeletal changes, as well as the activation of GTPase proteins and signaling kinases, were analyzed. RESULTS: Most NHOK cells in culture were polygonal, with only <5% cells exhibiting fibroblastoid morphology. However, 10 microg/ml ANE elicited fibroblastoid morphological change, genesis of lamellipodia, loss of subcortical actin, and stress-fiber formation in approximately 25% cultivated NHOK cells. Similar morphological changes were observed in nearly all OECM-1 cells following the ANE treatment. The activation of Rac and Rho GTPase, together with the prominent phosphorylation of a stress-activated kinases, particularly JNK1, was identified in treated OECM-1 cells. CONCLUSION: The novel evidences from the study that ANE impairs the actin organization and activates the signals in oral keratinocytes might bestow further insight into the impacts of ANE in oral pathogenesis.

Actins↗
PubMedDate not supplied

The relationship between areca nut usage and heart rate in lactating Bangladeshis.

BACKGROUND: The betel-nut quid, a piece of areca nut chewed alone or mixed with tobacco and slaked lime wrapped in betel vine leaf, is widely used in Asian populations as a stimulant (due to the cholinergic agent, arecoline) or as a relaxant (due to arecaidine and guvacine). OBJECTIVES: This study, which formed part of a larger project assessing the effect of energy expenditure on the duration of post-partum amenorrhoea, provided the opportunity to assess the role of chronic areca nut usage on heart rate and oxygen consumption during resting periods and during graded stepping tests. SUBJECTS AND METHODS: The mothers (n = 47), all of whom were lactating, were aged between 19 and 39, of low nutritional status and anaemic and they all chewed betel quid daily. RESULTS: Moderate users of betel quid (defined as more than 3 times a day) were found, on average, to have a significantly lower heart rate at rest and during exercise than low betel quid users (less than 3 times a day) but there was no modification in oxygen consumption. CONCLUSION: Chronic betel quid use does not seem to affect the assessment of 24h energy expenditure provided that subjects are denied access to betel nut usage before and during calibration.

Adult↗
PubMed1990

Effect of lime composition on the formation of reactive oxygen species from areca nut extract in vitro.

Lime, representative of that used by betel quid chewers, was collected in a region of Papua New Guinea where the incidence of oral cancer is high. The free calcium hydroxide content and pH of 25 lime samples were highly correlated with the generation of reactive oxygen species from areca nut extract in vitro, and DNA damage in vitro, measured as 8-hydroxy-2'-deoxyguanosine. Fe2+ and Mg2+ levels in the lime samples were too low to modify formation of reactive oxygen species, but hydrogen peroxide formation was almost entirely inhibited by addition of Mg2+ to the reaction mixture. These results suggest that the calcium hydroxide content of lime in the presence of areca nut is primarily responsible for the formation of reactive oxygen species which might cause oxidative damage in the DNA of buccal mucosa cells of betel quid chewers.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential.

There are 600 million betel quid (BQ) chewers in the world. BQ chewing is a major etiologic factor of oral cancer. Areca nut (AN) and arecoline may inhibit the growth of oral mucosal fibroblasts (OMF) and keratinocytes. In this study, AN extract (100-800 microg/ml) and arecoline (20-120 microM) inhibited the growth of oral KB cells by 36-90 and 15-75%, respectively. Exposure to arecoline (> 0.2 mM) for 24 h induced G(2)/M cell cycle arrest of OMF and KB cells. Areca nut extract (> 400 microg/ml) also induced G(2)/M arrest of KB cells, being preceded by S-phase arrest at 7-h of exposure. No evident sub-G(0)/G(1) peak was noted. Marked retraction and intracellular vacuoles formation of OMF and KB cells were observed. Glutathione (GSH) level, mitochondrial membrane potential (Deltabetam) and H(2)O(2) production of KB cells were measured by flow cytometry. GSH level [indicated by 5-chloromethyl-fluorescein (CMF) fluorescence] was depleted by 24-h exposure of KB cells to arecoline (0.4-1.2 mM) and AN extract (800-1200 microg/ml), with increasing the percentage of cells in low CMF fluorescence. By contrast, arecoline (0.1-1.2 mM) and AN extract (800-1200 microg/ml) induced decreasing and increasing H(2)O(2) production (by 2',7'-dichloro- fluorescein fluorescence), respectively. Hyperpolarization of Deltabetam (increasing of rhodamine uptake) was noted by 24-h exposure of KB cells to arecoline (0.4-1.2 mM) and AN extract (800-1200 microg/ml). AN extract (100- 1200 microg/ml) and arecoline (0.1-1.2 mM) induced little DNA fragmentation on KB cells within 24 h. These results indicate that AN ingredients are crucial in the pathogenesis of oral submucous fibrosis (OSF) and oral cancer by differentially inducing the dysregulation of cell cycle control, Deltabetam, GSH level and intracellular H(2)O(2) production, these events being not coupled with cellular apoptosis.

Apoptosis↗
PubMed1994

Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan.

A case-control study on chewing and smoking habits and oral submucous fibrosis (OSF) was undertaken in Karachi in 1989/90. Cases were patients detected with fibrous bands and leathery mucosa and hospital-based controls were matched by age and sex. Information on habits was collected by personal interview of 157 cases and 157 controls. Despite overall female preponderance, a substantial number of young men were enlisted. The male/female risks were found to be similar. Immigrants from India to Pakistan (Mohajir) had a similar risk status to local Punjabis. No differences between risks were found when comparing the three age categories, 21, 21-40, 41-60 yr. Among the cases, an increased risk was observed for areca nut chewing. This habit when practised alone appeared to have the highest risk (RR 154), followed by pan with or without tobacco (RR 64, 32 respectively). Logistic regression and discriminant analysis showed that daily consumption rates appeared to be more important with respect to risk than lifetime duration of habit. Tobacco habits were more prevalent amongst those 15 cases who presented with concurrent carcinoma and OSF: We conclude that areca nut chewing has a causal relationship with OSF: additional tobacco insult may be necessary for subsequent carcinoma development.

Adult↗
PubMed1994

Observations on the effect of areca nut extracts on oral fibroblast proliferation.

The effects of aqueous extracts of raw, baked and boiled areca nuts were tested on cultured human buccal mucosa fibroblasts. Cells were exposed to extract concentrations of 0, 50, 100, 150, 300 and 500 micrograms/ml. The arecoline and arecaidine content was determined in the extracts with HPLC and raw nut contained 5.5% m/m, baked nut 6.6% m/m and boiled nut 7.1% m/m. Extract concentrations of 50 to 150 micrograms/ml inhibited cell growth in a concentration-dependent manner but did not lead to total cell death during a 7 day period. However, total cell death did occur with concentrations of 300 and 500 micrograms/ml. It is concluded that areca nut extract is toxic to cultured fibroblasts and inhibits their proliferation in a concentration-dependent manner.

Areca↗
PubMed2006

The functional (-1171 5A-->6A) polymorphisms of matrix metalloproteinase 3 gene as a risk factor for oral submucous fibrosis among male areca users.

BACKGROUND: Insertion/deletion (-1171 5A-->6A) polymorphisms in the promoter region of matrix metalloproteinase 3 (MMP3) gene result in different transcriptional activities. MMP3 is able to degrade collagens types II, V, IX, and X, and other extracellular matrix. The functional promoter polymorphism of MMP3 has been related to the susceptibility in some inflammatory diseases and metastasis of cancers. METHODS: Oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) are prevalent among Asian areca users. In this study, genomic DNA obtained from the blood of OSCC (n = 150), OSF (n = 71), and control non-diseased areca user (n = 98) in male were subjected to polymerase chain reaction (PCR)-based genotyping of MMP3. RESULTS: The 5A genotype in MMP3 promoter was observed more frequently in OSF group than in control group (P = 0.01). No significant difference was noted between OSCC and control groups on the 5A genotype frequency (P = 0.18). No association was found between 5A genotype in MMP3 promoter and site or lymph node metastasis and stage of OSCC. CONCLUSION: The results indicated that the 5A genotype of MMP3 promoter was associated with the risk of OSF but not OSCC.

Adenine↗
PubMed1976

Treatment of Taenia saginata infection with mixture of areca nuts and pumpkin seeds.

In January and February 1974, 32 adults (20 males and 12 females) and a 13-year-old girl with taeniasis saginata were treated with the mixture of boiled areca nuts and pumpkin seeds at Mastoban, Jen-ai District, Nantou County, Taiwan. A total of 48 worms including 42 scolices were recovered from 29 cases. Side-effects were observed in 4 cases including 3 with complaints of dizziness, tinnitus, nausea and vomiting, and one with coma and abdominal pain. Mixtures of 75-150 g areca nuts and 50-100 g pumpkin seeds were judged effective and safe.

Adolescent↗
PubMed1997

[Experimental study on aqueous areca nut extracts inducing oral submucous fibrosis in rats. II. Effection of mast cells on collagen metabolism].

The effection of mast cells (MC) on collagen metabolism of oral submucous fibrosis (OSF) induced by aqueous areca nut extracts (AANE) in rats was studied by transmission electron microscope, histochemical and biochemical analyses. The results revealed that there was a close relationship between MC and fibroblats (FB) in the pathogensis of OSF; MC which appeared in the buccal mucosa in the model groups increased significantly and became more active in the function. A great deal of collagen compacted in the buccal mucosa in the model groups. The contents of tissue hydroxyproline (Hyp) in the model groups were obviously higher than those in the control groups. Moreover, the longer the time of irritation continued, the higher the contents were. The number of MC had a higher positive correlation with the contents of tissue Hyp at the same time. Total serum Hyp had no significant difference among all the groups and any stages. The results indicated that some aqueous components of areca nuts might disturb collagen metabolism by accumulation and activation of MC.

Animals↗