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Epidemiology of Cancer by Tobacco Products and the Significance of TSNA
Published in Roger O. McClellan, Critical Reviews in Toxicology, 2017
Prakash C. Gupta, P. R. Murti, R. B. Bhonsle
Evidence indicates63 that arecoline, which is a major alkaloid in areca nut, also yields nitrosamines such as MNPN, MNPA, N-nitrosoguvacoline (NG), and N-nitrosoguvacine (NGC). MNPN induces benign and malignant tumors of the esophagus, tongue, nasal cavity, and liver of rats. It alkylates DNA in vitro and in vivo to 7-methulguanine, O6-methylguanine, 7-(2-cyanoethyl guanine, and O6-(2-cyanoethyljguanine. Thus, while the experimental evidence for carcinogenecity of tobacco is very strong, for the areca nut it is indicative but perhaps not yet confirmatory.
Overview of biological mechanisms of human carcinogens
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Nicholas Birkett, Mustafa Al-Zoughool, Michael Bird, Robert A. Baan, Jan Zielinski, Daniel Krewski
Betel quids that contain tobacco products would pose the same carcinogenic hazards as described for smokeless tobacco. In addition, other components of betel quid, such as arecoline, areca nut, betel leaf, slaked lime, and catechu, were examined for carcinogenesis. Secondary and tertiary amines in betel quids may be converted to nitrosamines in the saliva and stomach. There is no evidence that the non-tobacco components of betel quid directly induce DNA damage. However, irritation of oral tissues from the quid, combined with the generation of reactive oxygen species, produce indirect DNA damage. Slaked lime produces a high-pH environment that exacerbates these effects. Increased frequencies of micronuclei were detected in oral exfoliated cells in chewers of betel quid without tobacco. Micronucleus formation was also observed in precancerous lesions in the oral cavity of chewers of betel quid alone, and of betel quid with tobacco. Elevated levels of sister chromatid exchange and micronucleus formation were observed in cultured peripheral lymphocytes collected from chewers of areca nut without tobacco and slaked lime, and with tobacco. DNA strand breaks were induced in both animal and human cell cultures. TP53 is downregulated and the function of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) altered.