Mutagenic activation of betel quid-specific N-nitrosamines catalyzed by human cytochrome P450 coexpressed with NADPH-cytochrome P450 reductase in Salmonella typhimurium YG7108

Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress

“…It is known that thiol depletion as well as ROS attack should be mainly responsible for arecoline-induced hepatoxicity (Dasgupta et al, 2006;Chang et al, 2001), and CYP enzymes play critical roles in mutagenic activation of the areca-specific N-nitrosamines (Miyazaki et al, 2005). The present work found that AH (4 and 20 mg/kg/d) significantly increased the hepatic CYP2E1 activity.…”

Arecoline inhibits the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1A1 activation in human hepatoma cells

“…TCDD induces hydroxylase activity by increasing the transcription rate of CYP1A1 gene [31]. It is noteworthy that CYPs have been demonstrated to play critical roles in mutagenic activation of the areca-specific N-nitrosamines [12]. Chemical nitrosation of arecoline, one of the major alkaloids in areca nuts, leads to the formation of areca-specific Nnitrosamines such as 3- (N-nitrosomethylamino)propionitrile, 3-(N-nitrosomethylamino)propioaldehyde, N-nitrosoguvacoline, and N-nitrosoguvacine [32].…”

“…Arecoline has been shown to induce human buccal mucosal fibroblast proliferation and collagen synthesis in vitro [10,11]. Moreover, a recent study has revealed that cytochrome P450 (CYPs) efficiently activate betel quid-specific N-nitrosamines, thus resulting in mutagenic activation of the N-nitrosamines in S. typhimurium YG7108 [12]. 0304 Like most of persistent organic pollutants, the lipophilic and ubiquitous features of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can result in its bioaccumulation along food chains and ultimately in humans.…”

Association of Cytochrome P450 with Cancer Induced by Betel Quid (BQ): A Review

“…CYP2A6 was found to be the most efficient activator of 3-methylnitrosamino propionitrile (MNPN) followed by CYP1A1, and N-nitrosoguvacoline (NGL), was activated by CYP2A6. The genotoxicity of NGL was observed to be substantially lower than that of MNPN or 3-methylnitrosamino propionaldehyde (MNPA) 104 . CYP1A1 Exon7 polymorphism G/G genotypes are susceptible to BQ-related oral cancer and OPMDs 105 .…”

“…Located on human chromosome 19, CYP2A express at least 13 different isoenzymes, among which CYP2A6 metabolically activates the Nalkylnitrosamines, N-nitrosonornicotine, and 4-(methylnitrosamino) -1 -(3-pyridyl) -1 -butanone, which have relatively long alkyl chains 109,110 . Miyazaki et al first reported that CYP2A subfamilies play important roles in the mutagenic activation of AN-derived Nnitrosamines 104 .…”