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N
CH 3
Nicotine
N
C 2 H 5 OH
Alochol
Caffeine
Arecoline
CH 3
O
O
N
H 3 C
Figure 6.3 Most abused substances in the world.
lip tissues. The patient finds it difficult to open and close the mouth and move the
tongue. The disease also makes the tongue sensitive to spicy food and causes rigid-
ity of the lip [9] . Arecoline is the main alkaloid of arecanut, with a soluble feature
in water and alcohol. During betel chewing, the concentration of arecoline [10] was
reported to reach 140 μg/ml.
6.4 Biomarkers for Arecoline-Induced Damage
An understanding of the biochemical changes during areca consumption and the
associated gene changes for oral cancer helps to identify the biomarkers associated
with areca abuse. About 12 susceptible genes (five induced and seven repressed
genes, including glutathione synthetase) can potentially serve as biomarkers of
arecoline-induced damage in betel chewers. Expression changes of these genes
were increased in a dose-dependent manner in a concentration range of arecoline at
50-150 μg/ml. To detoxify the arecanut and related ingredients, two monooxygenase
systems (cytochrome P450 and flavin-containing monooxygenases) are considered
important [11] . The free copper content was shown to high in arecanut ingredi-
ents [12] , and increased soluble copper levels are found in saliva of chronic chew-
ers. Copper acts as an initiating factor in oral carcinogenesis by stimulating fibrosis
through up-regulation of lysyl oxidase enzyme activity [13] .
The level of 8-hydroxydeoxyguanosine (8-OH-dG) in urine is an old known indi-
cator of carcinogenesis; similarly, serum arecoline and arecaidine levels are proven
 
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