Arecanut - Genomics of Cultivated Palms - page 66

to be good candidates for biomarkers for recent betel quid use [14] . Endogenous glu-
tathione (GST) and the level of p52 protein are also proved as biomarkers for raw
betel nut genotoxicity [15] . Arecoline-dependent avβ6 (alphavbeta6 integrin) up-
regulation promoted keratinocyte migration and carcinogenesis. In more than 80% of
oral cancers examined, there was moderate to high avβ6 expression [16] . Individuals
having a long history of areca consumption sometimes do not develop oral cancers.
Genetic polymorphism studies can be done to classify individuals according to their
response to arecoline-induced carcinogenesis. Screening of patients for SNPs in the
biomarker genes discussed above and correlating these data of carcinogenesis would
help to understand which individuals or groups are likely to be not affected by areca
consumption.
6.5 Xenobiosis, Metabolomics, and Pharmacogenomics
Pharmacogenomics is the study of genes and the gene products (proteins) essential
for pharmacological or toxicological responses to pharmaceutical agents. Xenobiosis
is a natural response to foreign compounds that elicits initiating signals for the
many physiological events after pathogenesis. Metabolomics is a methodology for
measuring small molecule metabolite levels and flux in biological matrices follow-
ing genetic modifications or exogenous challenges. Metabolic maps are extensively
investigated in other abused substances such as nicotine. Recently, metabolic maps
of arecoline and arecaidine [17-19] were developed, which are helpful in under-
standing the clinical toxicology of areca alkaloids [17] , especially 13 metabolites.
These are mostly novel such as unchanged  arecoline-1-oxide (50%), N-oxide
metabolites (25%), and mercapturic acids. Arecoline on hydrolysis yields arecaidine
that on nitro-oxidation forms mercaptauric acid [18] . Liquid chromatography-mass
spectrometry (LC-MS), coupled with in vivo metabolism of several xenobiotics, is
very efficient in identifying metabolites and elucidating in vivo metabolic pathways
and overall metabolic maps [19] . Recently, the possible role of arecoline N-oxide in
the induction of oral carcinogenesis by arecanut chewing was predicted due to its
mutagenicity to the Salmonella tester strains [20] . A toxicogenomic [21] database
for rANE (ripe arecanut extract) has been established using the down-regulation of
KGF-1 expression data in oral fibroblast cell lines potentially impairing the prolif-
eration of overlying keratinocytes. It partially explains the frequent epithelial atrophy
observed in chronic areca chewers in vivo . Such database and resources offer scope
in computational pharmacogenomic investigations using bioinformatics tools.
6.6 Areca Damage and Herbal Remedies
Arecanut has wide pharmacological properties as an antioxidant, anti-appetite, anti-
bacterial, anti-venom, antihelmintic, and molluscicidal, hence must be appropriately
used (review:23) at effective doses. Areca is a rich source of [22] tannins (8-18%)