Sequential Histologic Alterations of Mouse Gastric Mucosa Following Long-Term Simulation of Betel Addiction

Widespread tannin intake via stimulants and masticatories, especially guarana, kola nut, betel vine, and accessories.

Abstract: Tannins are increasingly recognized as dietary carcinogens and as anti-nutrients interfering with the system’s full use of protein. Nevertheless, certain tannin-rich beverages, masticatories, and folk remedies, long utilized in African, Asiatic, Pacific, and Latin American countries, are now appearing in North American sundry shops and grocery stores. These include guarane (Paullinia cupana HBK.) from Brazil, kola nut (Colanitida Schott &, Endl. and C. acuminata Schott &, Endl.) from West Africa, and betel nut (Areca catechu L.) from Malaya. The betel nut, or arecanut, has long been associated with oral and esophageal cancer because of its tannin content and the tannin contributed by the highly astringent cutch from Acacia catechu L. and Uncaria gambir Roxb. and the aromatic, astringent ‘pan’ (leaves of Piper betle L.) chewed with it. In addition to the constant recreational/social ingestion of these plant materials, they are much consumed as aphrodisiacs and medications. Guarane and kola nut enjoy great popularity in their native lands because they are also rich in caffeine, which serves as a stimulant. Research and popular education on the deleterious effects of excessive tannin intake could do much to reduce the heavy burden of early mortality and health care, especially in developing countries.

Inhibition of clastogenic effects of nicotine by chlorophyllin in mice bone marrow cells in vivo

Abstract: The effect of chlorophyllin in modifying the clastogenic action of nicotine was tested in vivo on mice bone marrow cells. Nicotine, when administered by gavage, induced chromosomal aberrations in frequencies directly proportional to the dose. Maximum effects were recorded at 6 h after exposure. Chlorophyllin, when given alone, was not clastogenic even at the highest concentration (1.50 mg/kg body wt). Simultaneous administration of nicotine and chlorophyllin with even lower doses (1.25 and 0.77 mg/kg body wt) reduced the frequency of chromosomal aberrations to the normal level. Chlorophyllin alone, given 2 h before nicotine, however, did not counteract the effects of nicotine. The use of green plant parts in modifying the genotoxicity of different agents may be related to the protective action of chlorophyllin.

Betel Cytotoxicity: Further Evidence from Mouse Bone Marrow Cells

Abstract: Long term studies (up to 10 months) for the simulation of betel habits, with or without tobacco, as currently practiced in Oriental countries, were performed using inbred Swiss albino mice. The cytotoxic and clastogenic potential of these complex chewing mixtures were assessed distally on bone marrow cells. Total aqueous extracts of Areca catechu L. nut and Nicoliana tabacum L. sundried leaf have been found to be mitogenic. The basic ingredients of the quid per se were not clastogenic. Tobacco, in any combination of chewing mixture, induced time-dependent clastogenicity. Direct damage to chromosomes was observed in the early stage, and lethal effects were observed in the latter stages of the study. Nuclear DNA content of the cells, measured in situ by Feulgen cytophotometry, was increased after administration of A. catechu and Piper betle leaf (vars. Bangla and Metha-Thakpala) or any combination of tobacco with or without leaf; nut and lime [Ca(OH)2]. High lime and leaf (var. Bangla) counteracted ...

Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid

Abstract: In order to evaluate exposure of betel quid chewers to N-nitroso compounds, saliva and urine samples were collected from chewers of betel quid with or without tobacco, from tobacco chewers, from cigarette smokers and from people with no such habit, and were analysed for the presence of N-nitrosamines by gas chromatography coupled with Thermal Energy Analyzer and alkaloids derived from betel nut and tobacco by capillary gas chromatography fitted with nitrogen-phosphorous selective detector. The levels of the betel nut-specific nitrosamines, N-nitrosoguvacoline and N-nitrososoguvacine (the latter being detected for the first time in saliva), ranged from 0 to 7.1 and 0 to 30.4 ng/ml, respectively. High levels of tobacco-specific nitrosamines were detected in the saliva of chewers of betel quid with tobacco and in that of chewers of tobacco, ranging from 1.6 to 59.7 (N'-nitrosonornicotine), 1.0 to 51.7 (N'-nitrosoanatabine) and 0 to 2.3 [4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone] ng/ml. Urinary concentrations of certain N-nitrosamino acids, including N-nitrosoproline, were determined as a possible index of exposure to nitroso compounds and their precursors in the study groups: no clear difference was observed. The betel nut-specific alkaloid, arecoline, was present at high levels in the saliva of betel quid chewers with or without tobacco. Nicotine and cotinine were also detected in saliva and urine of chewers of tobacco and of betel quid with tobacco. In order to assess whether N-nitroso compounds are formed in vivo in the oral cavity during chewing or in the stomach after swallowing the quids, the levels of N-nitroso compounds in betel quid extracts were determined before and after nitrosation at pH 7.4 and 2.1. The results indicate that N-nitroso compounds could easily be formed in vivo. The possible role of N-nitroso compounds in the causation of cancer of the upper alimentary tract in betel quid chewers is discussed.

3-(Methylnitrosamino)propionitrile: Occurrence in Saliva of Betel Quid Chewers, Carcinogenicity, and DNA Methylation in F344 Rats

Abstract: 3-(Methylnitrosamino)propionitrile (MNPN), a potent carcinogen in F344 rats, was detected for the first time in the saliva of betel quid chewers at levels ranging from 0.5 to 11.4 micrograms/liter. The tumorigenic properties of MNPN and its potential to methylate DNA in F344 rats were evaluated. Groups of 21 male and 21 female rats were given 60 s.c. injections over a 20-week period (total doses 0.055 and 0.23 mmol per rat). The experiment was terminated after 106 weeks. MNPN at the higher dose induced 18 (86%) malignant tumors of the nasal cavity in male and 15 (71%) in female rats. The lower dose induced nine (43%) liver tumors. Groups of four or five male F344 rats were treated with a single s.c. or i.v. injection of MNPN (0.4 mmol/kg). MNPN was also administered to rats by swabbing the oral cavity (2.21 mmol/kg). The levels of 7-methylguanine and O6-methylguanine, formed 0.5-36 h after treatment, were measured in the liver, nasal mucosa, esophagus, and oral issues. The highest levels of methylated guanines were detected in the nasal cavity independent of the route of administration. The results of this study demonstrate that MNPN is present in the saliva of betel quid chewers and is a potent carcinogen in F344 rats.

A study of betel quid carcinogenesis. IV. Analysis of the saliva of betel chewers: a preliminary report.

Abstract: Betel quid chewing is strongly associated with cancer of the oral cavity, especially when tobacco is added to the quid. It is our working hypothesis that, during chewing, Areca-derived N-nitrosamines are formed and, in the presence of tobacco, Nicotiana-specific N-nitrosamines are formed as well and further that these agents may contribute to the high risk of oral cancer in betel-quid chewers. This preliminary report presents our finding of N-nitrosoguvacoline in the saliva of betel-quid chewers (2.2–350 ppb). When the quid contains tobacco, the tobacco-specific N-nitrosamines, N′-nitrosonornicotine (1.2–38.3 ppb), N′-nitrosoanatabine (3.2–39.5 ppb), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (1.0–2.3 ppb) are also found in the saliva.