Because betel quid chewing has been linked to the development of
oral cancer, pathobiological effects of an aqueous areca nut extract, four areca nut
alkaloids (
arecoline,
guvacoline,
guvacine, and
arecaidine), and four nitrosated derivatives [
N-nitrosoguvacoline,
N-nitrosoguvacine, 3-(N-nitrosomethylamino)propionaldehyde and 3-(N-nitrosomethylamino)
propionitrile] have been investigated using cultured human buccal epithelial cells. Areca nut extract in a dose-dependent manner decreases cell survival, vital
dye accumulation, and membrane integrity, and it causes formation of both
DNA single strand breaks and
DNA protein cross-links. Depletion of cellular free low-molecular-weight
thiols also occurs, albeit at quite toxic concentrations. Comparisons of the areca nut-related N-
nitroso compounds and their precursor
alkaloids, at concentrations up to 5 mM, indicate that 3-(N-nitrosomethylamino)propionaldehyde is the most potent on a molar basis to decrease both survival and
thiol content and to cause significant formation of
DNA single strand breaks.
Arecoline,
guvacoline, or
N-nitrosoguvacoline decreases survival and cellular
thiols, whereas
arecaidine,
guvacine,
N-nitrosoguvacine, and 3-(N-nitrosomethylamino)propionitrile have only minor effects on these variables. Taken together, the present studies indicate that aqueous extract and, in particular, one N-nitroso compound related to areca nut, i.e., 3-(N-nitrosomethylamino)propionaldehyde, are highly cytotoxic and genotoxic to cultured human buccal epithelial cells, of potential importance in the induction of
tumors in betel quid chewers.