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8/12/2019 The Oral Health Consequences of Chewing Areca Nut
1/11
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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118 C. R. Trivedy etal.
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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Oral health consequences of chewing areca nut 119
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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120 C. R. Trivedy etal.
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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Oral health consequences of chewing areca nut 121
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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122 C. R. Trivedy etal.
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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