The Oral Health Consequences of Chewing Areca Nut

8/12/2019 The Oral Health Consequences of Chewing Areca Nut

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ISSN1355-6215print/ISSN1369-1600online/02/010115-11

SocietyfortheStudyofAddictiontoAlcoholandOtherDr ugs CarfaxPublishing,Taylor&FrancisLtd

DOI:10.1080/13556210120091482

Addiction Biology (2002)7,115125

Correspondence to: Prof. S.Warnakulasuriya, Department of Oral Pathology and Medicine, Kings Dental

Institute,DenmarkHillCampus,LondonSE59RW,UK.

ARECA NUT SYMPOSIUM

The oral health consequences of chewing arecanut

C.R.TRIVEDY,1G.CRAIG2&S.WARNAKULASURIYA1

1Department of Oral Pathology and Medicine, WHO Collaborating Center for Oral Cancer and

Precancer, The Guys, Kings and St Thomas Medical and Dental Schools of Kings College,

London & 2Department of Oral Pathology, School of Clinical Dentistry, Sheffield, UK

Abstract

Deleterious effects of areca nut on oral soft tissues are published extensively in the dental literature. Its effects

on dental caries and periodontal tissues, two major oral diseases, are less well researched. Areca-induced

lichenoid lesions mainly on buccal mucosa or tongue are reported at quid retained sites. In chronic chewers a

condition known as betel chewers mucosa, a discoloured areca nut-encrusted change, is often found where the

quid particles are retained. Areca nut chewing is implicated in oral leukoplakia and submucous fibrosis, both

of which are potentially malignant in the oral cavity. Oral cancer often arises from such precancerous changes

in Asian populations. In 1985 the International Agency for Research on Cancer concluded that there is limited

evidence to conclude that areca chewing may directly lead to oral cancer. There is, however, new information

linking oral cancer to pan chewing without tobacco, suggesting a strong cancer risk associated with this habit.

Public health measures to quit areca use are recommended to control disabling conditions such as submucous

fibrosis and oral cancer among Asian populations.

Introduction

Arecanutmaybeconsumedeitheronitsownor

morecommonlyinassociationwithother ingre-

dientssuchas tobacco, lime, catechu and other

spiceswrappedinabetelleafandreferredtoasa

betelquidorpan.1Recentlythetrendhasbeento

chew processed areca products known as pan

masalas. These contain a mixture of areca,

catechuandslakedlimeandmayalsoonoccasion

containtobacco.

Chewingarecanutonahabitualbasisisknown

to be deleterious to human health.2 A growing

bodyofevidenceoverthelast40years,mainlyin

the form of large-scale epidemiological andexperimentalstudies,hasshownthatevenwhen

consumedintheabsenceoftobaccoorlimeareca

mayhavepotentiallyharmfuleffectsontheoral

cavity. These effects can be divided into two

broadcategories:thoseaffectingthedentalhard

tissues, which include teeth, their supporting

periodontium and the temporomandibular joint

andthesofttissues,whichmakeupthemucosa

thatlinestheoralcavity.

Effects on hard tissues

Dental attrition

Themaineffectsofarecaonthehardtissuesare

ontheteeth.Thehabitualchewingofarecamayresultinseverewearofincisalandocclusaltooth


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116 C. R. Trivedy etal.

surfaces, particularly the enamel covering.The

loss of enamel may also expose the underlying

dentineandasthisissofterthanenamelwearsat

an increased rate.The exposure of dentine may

also result in dentinal sensitivity.The degree of

attritionisdependentuponseveralfactors,which

include the consistency(hardness) of the areca,thefrequencyofchewingandthedurationofthe

habit. Root fractures have also been demon-

stratedinchronicarecachewersandthisislikely

tobeaconsequenceoftheincreasedmasticatory

loadthatisplacedupontheteethandisnotdirect

effectofareca.3

Areca staining

Amongarecachewers,extrinsicstainingofteethdue to areca deposits is often observed partic-

ularly when good oral hygiene prophylaxis is

lacking and where regular dental care is

minimal.

Dental caries

It has been suggested that areca chewing may

confer protection against dental caries. Epide-

miologicalstudiescarriedoutinSouthEastAsiasuggest that the prevalence of dental caries in

areca chewers is lower than in non-chewers.46

Some investigators, however, have shown that

thereisnodifferenceintheprevalenceofdental

cariesbetweenarecachewersandnon-chewersin

other Asian populations.7,8 Although little is

knownaboutthecariostaticpropertiesofarecait

has been suggested that the betel stain, which

oftencoatsthesurfaceoftheteeth,mayactasa

protectivevarnish.9Thereisalsoin vitroevidence

thatsuggeststhatthetannincontentofarecamay

haveantimicrobialpropertiesandthismaycon-

tribute to the cariostatic role of areca.10 In

addition, chronic chewers also have marked

attrition of cusps of teeth leading to loss of

occlusalpitsandfissures,whichmayreducethe

risk of pit and fissure caries by eliminating

potentialstagnationareas.Theincreasedproduc-

tionofscleroseddentine inresponsetoattrition

mayconferprotectionagainstmicrobialinvasion.

Furthermore, theprocessofchewingitselfbringscopiousamountsofsalivatothemouthandinthe

presence ofadded slaked lime may increase the

pH in the oral environment; this may act as a

bufferagainstacidformedinplaqueonteeth.

Temporomandibular joint (TMJ)pathology

Themasticatoryforcesgeneratedduringchewing

areca may be transmitted to the TMJ and

subsequently may give rise to joint arthrosis.

However,thereisnoreliabledatatosubstantiate

anincreasedprevalenceinarecausersandfurther

studies are required. Furthermore, symptomssuch as trismus are common to both TMJ

pathologyandtootheroraldisordersassociated

with areca chewing such as oral submucous

fibrosis.Itisdifficulttodistinguishadirecteffect

ontheTMJfromthefibroticinvolvementofthe

oral musculature that may contribute to limita-

tionofmouthopeninginchronicchewers.

Effects on soft tissues

Periodontal disease

In vitro studies have demonstrated that areca

extracts containingarecoline inhibit growth and

attachment of, and protein synthesis in, human

culturedperiodontalfibroblasts.11,12Onthebasis

of these findingsthe investigatorsproposed that

arecamaybecytotoxictoperiodontalfibroblasts

andmayexacerbatepre-existingperiodontaldis-

easeaswellas impairperiodontalreattachment.

Some investigators have shown that loss of

periodontalattachmentandcalculusformationisgreaterinarecachewers.13However,itisdifficult

to interpret such studies, as there are several

confounding variables such as the level of oral

hygiene,dietaryfactors,generalhealthandden-

tal status, not to mention tobacco smoking,

whichmayhaveasignificantinfluenceonperio-

dontal status. Furthermore, as the majority of

chewers are in the Indian subcontinent, where

oral health education is limited, periodontal

health may be compromised even in non-areca

chewers. It is therefore difficult to ascertain the

biological effects of areca on periodontal health

butinviewoftherecentin vitroevidencefurther

clinicalandexperimentalstudiesarenecessary.

Lichenoid lesions

Areca-inducedlichenoidlesions,mainlyonbuc-

calmucosaortongue,havebeenreportedatsites

ofquidapplication.14This isconsidered tobea

type IV contact hypersensitivity-type lesion butresemblesorallichenplanusclinically.Themain

detectablefeaturesarethatitisfoundatthesite

ofquidplacementinarecachewersandmaybe

unilateralinnature.Finewavykeratoticlinesare


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Oral health consequences of chewing areca nut 117

seen to radiate from a central red/atrophic area

and, interestingly, the keratotic striae do not

criss-cross and are parallel to each other. The

histologyissuggestiveofalichenoidreactionand

thelesion isnotedtoresolvefollowingcessation

ofarecause.

Betel chewers mucosa (BCM)

This condition was first described by Mehta et

al.15 and is characterized by a brownish-red

discolourationoftheoralmucosa.Thisdiscolour-

ationisoftenaccompaniedbyencrustationofthe

affected mucosa with quid particles, which are

not easily removed, and with a tendency for

desquamation and peeling.The underlying area

assumes a wrinkled appearance. The lesion is

usually localized and associated with the site ofquidplacementinthebuccalcavity.Thelesionis

associated strongly with the habit of betel quid

chewing,particularlyinelderlywomenwhohave

been chronic chewers for longdurations.16 Sev-

eralepidemiologicalstudieshaveshownthatthe

prevalence of betel chewers mucosa may vary

between0.2%and60.8%indifferentSouthEast

Asianpopulations(Table1).Histologically,betel

chewers mucosa shows epithelial hyperplasia,

which is encrusted with an amorphous deposit.

This reacts positively to von Kossa staining

suggestingthatthesegranules,whicharelocated

both intra- and intercellularly, may contain cal-

cium from the calcium hydroxide in slaked

lime.20Aballooningeffectoforalkeratinocytesis

noted. The presence of the human papilloma

virus(HPV)subtypes11,16and18hasalsobeen

demonstratedinBCMbutthesignificanceofthis

isnotfullyunderstood.21

Althoughtheexactmechanismsunderlyingthe

development of this condition are not fullyunderstood it is thought that the chemical and

traumatic effects of the betel quid on the oral

mucosamaybesignificantfactors.Furthermore,

thereisalsoevidencethatthepresenceoftobacco

inthequidisnotessentialforthedevelopmentof

BCM.22AtpresentBCMisnotconsideredtobe

potentially malignant, although the condition

oftenco-existswithothermucosallesionssuchas

leukoplakia and oral submucous fibrosis, which

are well known fortheir potential for malignant

change.

Oral leukoplakia

Leukoplakia can be defined as a predominantly

white patch or plaque on the oral mucosa that

cannot be characterized clinically or patholog-

ically as any other disease and is not associated

withanyotherphysicalorchemicalagentexcept

tobacco.23 Based on clinical appearance, leuko-

plakia can be divided into several subtypes:

homogeneous(white),speckled(red/white),nod-ularorverrucousleukoplakia.

Thisconditioniswellknownforitspotentialfor

malignant change and transformation rates

between0.1and17.5%havebeenquotedinthe

literature.24Thefiguresformalignanttransforma-

tion based on population studies reported from

India25 aremuchlowerthanthosereportedfrom

EuropeandtheUnitedStatesbasedonhospital

series, but this may be due to a selection bias.

Thereisalsoevidencethattheclinicalpresenta-

tion(siteandtype)mayinfluencetheriskpotential

formalignantchange.Thespeckledlesionscarrya

greaterriskformalignantchangeincomparisonto

thehomogeneouswhiteplaques.26

In biopsies in addition to the presence of an

amorphous brown-staining von Kossa positive

layeronthesurface,parakeratosisandatrophyof

thecoveringoralepitheliumarereportedinareca

chewers.27 Inanotherstudy,14%ofleukoplakia

biopsies obtained from areca chewers demon-

strated cellular atypia amounting to epithelialdysplasia.28 Histopathology of an areca nut-

associated oral mucosal lesion presenting clini-

cally as a white/red patch and demonstrating

severeepithelialdysplasiaisshowninFig1.

Table 1. Prevalence of betel chewers mucosa in different populations

Reference Country Year Number Prevalence%

16 Cambodia 1996 102 60.8

17 Malaysia 1995 850 21.9

18 Cambodia 1995 1319 < 1

19 Thailand 1987 1866 13.1


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Althoughthereisconsiderablecontroversyand

debateabouthowtodefineoralleukoplakiathere

islittledoubtthatbothtobacco,inanyform,and

arecanutusearemajorriskfactorsfordeveloping

this condition.29,30 In Ernakulum, India a

10-year follow-up study recorded that the inci-

denceofleukoplakiainagroupofchewers,which

consisted mainly of pan chewing, was 2.5 per

1000 people.25Warnakulasuriya31 reviewed four

casecontrolstudiesthatexaminedrelativeriskof

oralleukoplakiainbetelquidchewers.Inoneof

thestudies,chewingareca(inbetelquidwithout

tobacco) raised the odds ratio (OR) to 5 com-

pared with non-chewers (O R = 1); adding

tobaccotothequidfurtherraisedtherelativerisk

byatleastthreefoldcomparedwithnon-tobaccousers.32 More recently, the results of a case

controlstudyconductedinTaiwan,whereareca

ischewedwithouttobacco,foundtheoddsratio

for developing leukoplakia was 17.43 (95% CI

1.94156.27) for areca nut chewers.33 Fur-

thermore, the authors demonstrated that the

cessationofarecachewingresultedinresolution

of62%ofleukoplakias,suggestingthatarecaon

its own is a significant aetiological factor in the

developmentofleukoplakia.Furtherevidenceof

itsrelationshipwitharecachewinghascomefromthe increased prevalence of this condition in

subjectswhosufferfromoralsubmucousfibrosis,

which is associated strongly with the habit of

arecachewing.34

Oral submucous fibrosis (OSF)

Thisisachronicdisordercharacterizedbyfibrosis

oftheliningmucosaof theupperdigestivetract

involving the oral cavity, oro- and hypopharynx

and the upper third of the oesophagus.35 The

fibrosis involves the lamina propria and the

submucosaandmayoftenextendintotheunder-

lying musculature resulting in the deposition of

densefibrousbands,whichgiverisetothelimited

mouth opening which is a hallmark of this

disorder. Warnakulasuriya36 defined a series of

symptomsandsubjectivesignswhicharecharac-

teristic of OSF to be employed as the clinical

criteria required to make a diagnosis of OSF

(Table 2). This symptomatology of OSF wasadoptedataconsensusworkshopheld toclarify

thenomenclatureofarecaquid-associatedlesions

andconditions.1 HistopathologyofOSFisillus-

trated in Figs 2 and 3 in long-standing areca

chewers,withunderlying fibrosisof laminapro-

pria being the pathognomic feature. Epithelial

atrophyoftenassociatedwithOSFisseeninFig.2

andaccompaniedepithelialdysplasiainFig.3.

Thepotentiallymalignantnatureofthiscondi-

tion has been well documented. A malignant

transformationrateof7.6%overaperiodof10

Figure 1. Severe epithelial dysplasia in a `speckledleukoplakia ar ising in the lateral border of tongue mucosa in

a long-term tobacco and areca nut user; male aged 47 years;

H&E 100.

Table 2. Clinical features of OSF

Early Late

Blanchingofmucosa Fibrousbands

Intolerancetospicyf ood Tr ismus

Petechiae Flatteningofpalate

Depapillationoftongue Hockey-stickuvulaOralulceration Reducedtonguemobility

Leatherymucosa Xerostomia

Tastedisturbance Keratosis

Source:Refs1&36.


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yearswasdescribedinanIndiancohort37andthe

relativeriskformalignanttransformationmaybe

ashighas397.3.38

Although OSF was first described by

Schwartz39 inaseriesofIndianwomenlivingin

East Africa there are descriptions of a similar

conditionoccurringinbetelchewersinearlytexts

datingbackto1908.40 SinceSchwartzspublica-

tion,OSFhasbeendetectedinseveralepidemio-

logicalstudiesconductedmainlyinIndia,amongIndianslivinginsouthAfrica,amongChineseor

in other south Asian populations (Table 3). At

present there are few data on the prevalence of

OSF among Asians living in Europe and the

United States but there have been several case

reports, describing OSF in some habitues who

continue to chew areca following

migration.5052

It is now accepted that chewing areca is the

single most important aetiological factor for

developing OSF.53,54 Other causes which have

been proposed in the past but have not been

substantiated include excessive consumption of

chilies, autoimmune reaction and nutritionalfactors,particularlyirondeficiency.

Much of the evidence implicating areca has

been derived from epidemiological data arising

largely from India, Pakistan and South Africa.

ManyobservationalstudiesonOSFpatientshave

recorded a high frequency ofthe arecachewing

habit in the OSF subjects (close to 100%)

compared to that of the general popula-

Figure 2. (A)Epithelial atrophy and subepithelial fibrosis

extending into the underlying voluntary muscle fibres in the

buccal mucosa of 49 year-old male with a long history of oral

submucous fibrosis; H&E 10 (B) Epithelial atrophy

and subepithelial fibrosis in the floor of mouth mucosa from

a 43 year-old female with extensive oral submucous fibrosis

and a long history of both tobacco and areca nut usage;

H&E 50.

Figure 3. Severe epithelial dysplasia in the retromolar

mucosa of a 59 year-old female with oral submucous fibrosis

and a long history of both tobacco and areca nut usage; same

patient as shown in Fig. 2B but 16 years later; H&E

20.

Table 3. The global epidemiology of OSF

Country/Ref. Sampleno. Prevalence%

India

41 10 000 0.51

42 5000 1.22

43 10 071 0.16

44 35 000 0.59

45 101 761 0.070.4

46 5018 3.2

SouthAfrica47 1000 0.5

48 2058 3.4

China

49 11 046 3.03


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tion.48,49,55Severalcasecontrolstudieshavealso

shownthatthereisanincreasedriskofdevelop-

ing OSF in subjects consuming areca products

(Table4).Therelativeriskwasnotedtorisewith

an increasing frequency of the areca chewing

habit, suggesting a doseresponse relation-

ship.57,58Aninterventionalstudyconductedover

a 10-year follow-up period in India showed a

decrease in the incidence of OSF in the trial

cohortcomparedwithacontrolpopulationasa

result of cessation of areca use.60 However, the

authorspointoutthatOSFisemergingasannewepidemic in India due to rising trends in per

capitaarecaconsumption.46

Althoughthereisgoodevidencetosupportthe

role of areca as the major risk factor in the

developmentofOSF, the mechanismsbywhich

this occurs are not fully understood. In vitro

studieshaveshownthatarecanutalkaloidssuch

asarecolineanditshydrolysedproductarecaidine

may stimulate cultured fibroblasts to proliferate

and synthesize collagen.61,62 In addition fla-

vonoidswithinthenut havealso beenshownto

increase thestabilization of collagenbyenhanc-

ingthecross-linkingofcollagen,therebyincreas-

ing the resistance to degradation by collage-

nases.63 However, subsequent in vitro studies

havefailedtoshowsimilareffectsofarecolineon

cultured OSF fibroblasts.64,65 Furthermore,

recentstudieshaveshownthatarecolineinhibits

collagen synthesisand fibroblast proliferation in

vitro,suggestingthatarecolinemayhavecytotoxic

properties.12,66,67Thedisparityofresultsfrominvitro studiessuggeststhat thearecamaycontain

other agents in addition to arecoline which are

importantinthepathogenesisofOSF;theroleof

arecoline,therefore,needsfurtherevaluation.

There has been recent interest in the role of

copper in the pathogenesis of this disorder and

raisedcopperconcentrationshavebeenshownin

productscontaining arecanut incomparison to

othernut-based snacks.68 Chewingareca forup

to 20 minutes releases significant amounts of

soluble copper to the whole mouth fluid.69

Furthermore, there is evidence to show that

mucosal biopsies taken from OSFsubjects con-

tain a higher copper concentration than those

taken from controls.70 This has led to the

hypothesis that the increased tissue copper mayincreasetheactivityoftheenzymelysyloxidase,

which is a copper-dependent enzyme that has

been implicated in the pathogenesis of several

fibrotic disorders, including OSF.71,72 Further

supportforthistheorycomesfromstudieswhich

demonstrate that inorganic copper salts in vitro

significantly increase the production of collagen

byoralfibroblasts.73

Very few animal models of OSF have been

described. Khrime et al.74 demonstrated histo-

pathological changes consistent with OSF in

albinoratswhoseskinwassubjectedtorepeated

exposure to commercially available areca prod-

ucts. Earlier studies, however, found that the

application of arecoline to the palates of

B12-deficient rats did not give rise to any fea-

tures which were suggestive of OSF.75 Applica-

tion of arecaidine to hamster cheek pouch also

failed to show any microscopic changes sugges-

tive of fibrosis.76

The fact that only a small proportion ofsubjects who chew areca actually develop OSF

raisesthepossibilitythattheremaybeagenetic

predisposition for thisdisorder.There is limited

evidenceintheliteraturetosupportthatpeople

Table 4.Relative risk (RR)of developing of OSF in areca chewers

Reference Country Cases Controls Relativerisk(RR)

46 India 164 5018 60.6(areca)

75.6(Mawa)

56 India 200 200 489.1(panmasala)

136.5(areca)57 Pakistan 157 157 154.0(arecaonly)

64.0(betelquid + tobacco)

32.0(betelquid)

58 India 60 60 29.9(areca)

106.4(Mawa)

59 Taiwan 35 100 43.8(betelquid)


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ofBangladeshiorigindevelopOSFalthoughthey

indulge inarecahabits.HLAstudiesconducted

onOSFhaveshowndivergentresultsandastudy

ofacohortofUK-basedOSFpatientsfoundan

increased frequency of DR3, A10 and B7,77

whereasastudyconductedonaPakistanipopula-

tion found an increased frequency of CW2 and

DR1.78 Incontrast,studiesconducted inAsians

living inSouthAfrica foundnoHLA-associated

susceptibility in OSF.79 The evidence from the

literaturestronglyimplicatesarecaintheaetiopa-

thogenesis of OSF although further studies are

warrantedtouncoverthemechanismsunderlying

the pathological processes in relation to the

developmentofthefibrosisandtransformationto

squamous cell carcinoma, which can be con-

sideredasthemostseriousoralhealthsequence

of this disorder. Figure 4 illustrates a case of

squamous cell carcinoma arising in a case of

OSF.

Oral squamous cell carcinoma (OSCC)

Thereishistoricalevidencedatingbacknearlya

century that suggeststhat theareca nutmaybe

involved in the development of OSCC.40,80,81

Although itiswidelyacceptedthatthepresence

oftobaccoinbetelquidplaysanimportantrolein

thepathogenesisoforalsquamouscellcarcinoma

thecarcinogenicpotentialofarecaintheabsence

of other ingredients is less clear.82There are

epidemiological data from several casecontrol

studies thatconfirmthatthehabitofbetelquid

chewing increases therelativeriskofdeveloping

OSCC.83

The description of the chewing habithas not been explicit in some of these studies.

Some of the relevant studies with estimated

relativeriskarelistedinTable5.Thebulkofthe

dataintheliteraturesuggeststhattheadditionof

tobacco to the quid increases its carcinogenic

potential.8890 Areca (pan) chewing without

tobaccocausingoralcancerhasbeenhighlighted

in a few recent studies. In one South African

study,68%ofcheekcancersand84%oftongue

cancerswerefound insubjectsconsumingareca

without tobacco.87 Furthermore, there is new

evidencewhichsuggestthatarecaintheabsence

oftobaccomaybeanindependentriskfactorfor

thedevelopmentoforalSCC.84

Inadditiontohumandatatherearealsoalarge

number of experimental studies, which have

attemptedtoevaluatethecarcinogenicpotential

Figure 4. Micro-invasive, well-differentiated squamous cell

carcinoma arising in the ventral tongue mucosa of the

patient shown in Figs 2b and 3; now aged 63 years and still

using both tobacco and areca nut; H&E 25.

Table 5.Relative risk of developing oral squamous cell carcinoma (SCC)in relation to chewing habits

Reference Country Cases Controls Habit RR forSCC

33 Taiwan 60 100 Arecanut 3.79(95%CI1.2012.24)

84 Pakistan 79 149 Panwithtobacco 8.42

Panwithouttobacco 9.9

85 Taiwan 40 160 Betelquid* 58.4(95%CI7.6447.6)

Duration(years):120 17.1(95%CI1.8161.9)

2140 108.4(95%CI11.9987.9)

40 + 403.5(95%CI20.87843.0)

Frequency(/day)19 28.3(95%CI3.3240.7)

1020 61.9(95%CI7.9487.2)

> 20 294.1(95%CI16.5

5233.686 Taiwan 107 200 Betelquid* 123

87 SouthAfrica 143 735 Arecanut 43.9(95%CI18.6103.6)

Arecanut + tobacco 47.4(95%CI20.3110.5)

*ThebetelquidusedinTaiwanispredominantlyarecanutbased.


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of areca and its derivatives both in vivo and in

vitro.Jenget al.91 inarecentreviewexaminedthe

mutagenecityandgenotoxicityofarecaalkaloids

totargetcellsintheoralmucosa.

InvivostudiesSeveralanimalstudieshaveconfirmedthatareca

products and derivatives such as arecoline- and

areca- derived nitrosamines have the ability to

induceneoplasticchangesinexperimentalmod-

els. Early studies found that the application of

arecaidine to the oral mucosa of experimental

animals failed to have any carcinogenic effects,

butwhensupplementedwithaknownpromoter

suchascrotonoilresulted incellulardamage,76

whereasotherstudieshaveshownthattheappli-

cation of areca products to the oral mucosa of

animalsresultsinhistologicalchangeswhichmay

beindicativeofDNAdamage.92,93 Inadditionto

thelocaleffectsofarecaontheoralmucosathere

is also evidence that suggests that areca, when

appliedtotheskinofanimalmodelsorincluded

inthefeed,maycauseneoplasticchangesinsites

distant from the oral cavitysuchas the foregut,

liver,kidneysandlung.9497

Invitrostudies

Therearealsodataintheformofin vitrostudies

whichhavebeenconductedonChinesehamster

ovary(CHO)cellsandmammaliancelllinesthat

suggest thatareca extract maypossess cytotoxic

and genotoxic effects.67,98100 There are also

limiteddatafrommutagenicityassaysconducted

onbacteria(Staphyllococcus typhi)whichsuggest

that commercially available products containing

areca (pan masalas) have mutagenic

properties.101,102

Human studies

Amongarecachewerspossiblegenomicdamage

caused by areca nut (without tobacco) was

confirmedincytogenticstudies.103

Conclusion

Itisclearfromtheliteraturethatarecamayhavesignificanteffectsuponthehardandsofttissues

oftheoralcavity.Itsallegedbeneficialeffectson

dental caries and the possible damage to the

periodontiumneedfurtherevaluation.

Based onmanypopulation studies conducted

in Asia the role of areca in the pathogenesis of

betelchewersmucosa,oralleukoplakiaandoral

submucous fibrosus is well established. Both

leukoplakia and submucous fibrosis are poten-

tially malignant conditions in the oralcavity.At

the time of the last review by the InternationalAgencyforResearchonCancerin1985informa-

tion available on the carcinogenic role of areca

was limited.New informationfromseveralpop-

ulationstudies,however,suggestthatarecaonits

ownmayplayanaetiologicalroleinthecausation

of oral cancer. Public health education against

arecanutuseisessentialtocontroloralcancerin

emerging market economies and among Asian

migrant communities in other parts of the

globe.

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The Oral Health Consequences of Chewing Areca Nut