Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice.
Chewing the areca nut is carcinogenic to humans. Arecoline, a major alkaloid in areca nut, is suspected to be a carcinogenic component. It has been shown to have genotoxic potential in various in vitro systems; but information on its in vivo genotoxicity is limited. To investigate the organ-specific mutagenic potential of arecoline, we employed gpt delta transgenic mice to analyze the mutagenicity of arecoline in the oral tissues and liver. Male gpt delta mice were given arecoline hydrobromide in drinking water at 300 and 700μg/mL for 6 weeks. 4-Nitroquinoline-1 (4-NQO) was used as a positive control. Two weeks after the last treatment, mutation frequencies in the oral tissues (a mixture of gingival, buccal, pharyngeal and sublingual tissue) and liver were detected and mutation spectra were analyzed. There were no statistically significant differences in the average mutation frequencies between arecoline-treated and untreated groups in both the oral tissues and liver. However, in the oral tissues, one mouse in arecoline-300μg/mL group and two mice in arecoline-700μg/mL group showed more than 2.5-fold higher mutation frequencies than the untreated group; they also exhibited unique mutation spectra compared to spontaneous mutation types. In these three mice, all mutations occurred at G:C sites, where G:C→T:A transversions were most frequent, followed by G:C→A:T transitions and G:C→C:G transversions. The main type of spontaneous mutation in both the oral tissues and liver was G:C→A:T transition. These results suggest that arecoline poses a mutagenic hazard in the oral tissues of gpt delta transgenic mice.
Center for Drug Safety and Evaluation Research, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Mengjun
M
Wu
Guozhen
G
Xing
Xinming
X
Qi
Chenchen
C
Feng
Mingxia
M
Liu
Likun
L
Gong
Yang
Y
Luan
Jin
J
Ren
D000818:Animals; D001115:Arecoline / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D018679:Cholinergic Agonists / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009055:Mouth / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D059645:Mutation Rate
D018679:Cholinergic Agonists; D009153:Mutagens; D001115:Arecoline; D007041:Hypoxanthine Phosphoribosyltransferase