Arecoline N-Oxide: Its Mutagenicity and Possible Role as Ultimate Carcinogen in Areca Oral Carcinogenesis

Abstract

The areca nut is the most widely consumed psychoactive substance in Taiwan, India, and Southeast Asia. It is considered to be an environmental risk factor for the development of oral submucous fibrosis and cancer. Arecoline, the major alkaloid of areca nut, has been known to cause cytotoxicity and genotoxicity in various systems. However, the active compound accounting for arecoline-induced damage in normal human oral cells is still uncharacterized. The present study was undertaken to identify the active metabolite of arecoline that might induce damage in human oral tissues and cause mutagenicity in Salmonella typhimurium tester strains TA 100 and TA 98. It is interesting to find that the major metabolite of arecoline, arecoline N-oxide, is moderately mutagenic to these Salmonella tester strains. This mutagenicity was potently inhibited by sulfhydryl compounds, namely, glutathione, N-acetylcysteine, and cysteine, whereas methionine is inactive in this inhibition. The mutagenicity of arecoline N-oxide was strongly inhibited by the N-oxide reducing agent titanium trichloride. The possible role of arecoline N-oxide in the induction of oral carcinogenesis by areca nut chewing is discussed.

Fibrotic Effects of ArecolineN-Oxide in Oral Potentially Malignant Disorders

“…4 Previous studies identified that arecoline, arecaidine, guvacoline, and guvacine are the four major alkaloids among the chemical constituents of the areca nut. 5 Arecoline, the most abundant and active alkaloid, is suggested to be a potential carcinogen. 4 Besides its reported cytotoxic effects on cultured oral cells, studies with bacteria, mammalian cells, and experimental animals have revealed arecoline's mutagenic and genotoxic effects.…”

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice

“…It was reported to be mutagenic in Salmonella (TA100, TA1535, TA98 and TA1538), and the mutagenicity was enhanced in the presence of S9 (TA98 and TA 100) [14,15]. Another report suggested that arecoline was weakly mutagenic in TA98 and TA100 only under metabolic activation [16]. In mammalian cell mutagenicity assays, arecoline induced 8-azaguanine resistant mutation in Chinese hamster V79 cells [17] and increased chromosomal aberrations, sister-chromatid exchanges in Chinese hamster ovary (CHO) cells [18] and elicited ␥-H2AX phosphorylation and suppresses DNA repair [12].…”

Facile Synthesis and Characterization of Novel CdS/BiOI Heterojunctions with Enhanced Visible-Light Photocatalytic Performances

“…The broad bands centered at 3450 cm −1 and 1587 cm −1 in the spectrum of BiOI corresponded to the stretching and bending vibrations of O-H, respectively. Moreover, the band at 489 cm −1 for both samples of pure BiOI and CdS/BiOI nanocomposites was associated with the stretching vibrations of the Bi-O [30]. In comparison with the spectrum of BiOI, the weak absorption band at 618 cm −1 could be ascribed to the Cd-S group which was in the spectrum of the CdS/BiOI nanocomposites.…”