Histopathological effects of chewing of betel quid with tobacco was studied by simulating four different chewing habits, using mouse glandular stomach mucosa as a model system. Chronic oral administration for five months resulted in marked intestinal metaplasia in all animals receiving extract of tobacco with betel nut and lime and extract of tobacco with betel leaf, nut and lime, in doses normally ingested by human addicts. Tobacco markedly augmented the effect of other ingredients. Lime and Piper betle L. var. bangla probably played a protectant role by reducing the dysplasia and metaplasia. In the light of the growing use of smokeless tobacco and betel chewing habits, our results may exemplify the way in which the various chewing mixtures, which are ingested daily in relatively large quantities, could affect carcinogenesis in habitual chewers. © 1987 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

S SEN

G TALUKDER

A SHARMA

University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

&nbsp;

The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

&nbsp;

It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Potentiation of Betel-Induced Alterations of Mouse Glandular Stomach Mucosa by Tobacco in Studies Simulating Betel Addiction

Pharmaceutical Biology

Higher plants used extensively in traditional medicines are increasingly being screened for their role in modulating the activity of environmental genotoxicants. The property of preventing carcinogenesis has been reported in many plant extracts. The observation of a close association between carcinogenesis and mutagenesis has extended the survey to include plant extracts and plant products able to modify the process of mutagenesis, which involves alteration in the genetic material. Natural plant products may, apart from inducing mutations, modify the action of other known mutagens on the living organisms by 1) activating the existing mutagens within the cell, 2) inhibiting the production of mutagens in the cell, 3) synergising the activity of existing mutagens, or 4) activating the promutagens within the cell into mutagens. This review deals with data obtained in the course of research on the modulatory effects of plant extracts on mutagenesis and clastogenesis, two genotoxic phenomena associated with carcinogenesis. In screening for antimutagenic effects, extracts of different plant parts have been used, ranging from leafy vegetables, fruits, and underground storage organs to whole plants. The extracts were prepared mainly in water or organic solvents. Several of these assays have indicated the involvement of certain factors that are intrinsic components of the extracts, ranging from specific compounds like ascorbic acid to vegetable fibres which could act as nonspecific redox agents, free radical scavengers, or ligands for binding metals or toxic principles. The possible ways in which inhibitors of mutagenesis can act include the inhibition of interaction between genes and biochemically reactive mutagens and the inhibition of metabolic activation of indirectly acting mutagens. The effects of toxicants can be observed at the level of chromosomes (clastogenesis) through alterations in chromosome structure (chromosomal aberrations) and number (aneuploidy, polyploidy). A wide range of short-term and long-term screening procedures is available. The most common ones use higher plants or rodents in vivo as test systems for monitoring chromosomal aberrations. Experiments with a number of crude vegetable and fruit extracts have demonstrated their anticlastogenic activities against known cytotoxic agents. The individual components of the extracts - e.g., sulfhydryl and flavonoid compounds, gallic acid, ellagic acid, mucic acid, citric acid, reducing sugars, tannin - are observed to have an additive interaction with the major constituents chlorophyll and ascorbic acid, when modulating the effects of the clastogens. Under certain conditions, plant products may induce mutagenic effects, due to the presence of multiple biological properties. Some inhibitors can stimulate simultaneously both enhancing and detoxifying mechanisms, e.g., inducers of coordinated enzyme activities. Many oxidants can, depending on the redox potential, either accept or donate electrons, rendering them protective or harmful. Plants also play an active role in the accumulation, metabolism, and environmental distribution of xenobiotics. The property of plants to activate promutagens that may enter the food chain is of great significance in view of the large number and types of chemicals to which the plants are exposed. A promutagen is a chemical that is not mutagenic itself but that can be biologically transformed by a plant system into a mutagen. Several methods for studying promutagens from plants were developed both in vivo and in vitro, including plant cell-free systems. Both mutagens and antimutagens can be extracted from the same plant extract depending on the nature of solvents used for extraction. Interaction between inhibitors may lead to synergistic effects. Such combined action may take place through the different inhibitors acting at different levels or being localised at different cellular areas. The greater protection afforded by crude plant extract as compared with an equivalent amount of the purified or synthetic ingredients, as observed with Phyllanthus emblica L. and Beta vulgaris L. var. benghalensis Hort., may be related to this phenomenon. Specific biological action of a drug is due to its specific binding to a functional molecular receptor. In complex plant extracts, the variable observed effects can be attributed to the many chemically reactive species that are formed during the processing and ingestion of the extract, which could act as non-specific redox agents, scavengers of free radicals, and ligands for binding to toxicants. The final effects are obviously the outcome of interactions between the components and their individual and collective interaction with the toxicant. The specificity and efficacy of such responses will be influenced also by the physiological factors influencing the plants and the process of administration of the extract. In utilizing pharmacologically active herbs, both beneficial and potential adverse effects must be taken into account. The actual dose and form of the plant also need to be worked out.

Botanical Review

Plant Extracts as Modulators of Genotoxic Effects

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. Copyright © 1991 John Wiley & Sons, Ltd.

Phytotherapy Research

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

The antagonistic effect of chlorophyllin was tested in reducing the clastogenic action of cesium chloride (CsCl) in vivo on mice bone marrow cells. CsCl induced chromosomal aberration in frequencies directly proportional to the dose administered. Chlorophyllin, when given alone, was not clastogenic even at a concentration of 1.5 mg/kg body wt. of the animal. Simultaneous administration of chlorophyllin and CsCl reduced chromosomal aberrations significantly at 24 h. Exposure to the same dose of chlorophyllin 2 h before exposure to CsCl also decreased clastogenic effects but to a lesser extent. These findings are of importance in view of the uptake of radioactive Cs by green plants after nuclear fallout. © 1991.

Toxicology Letters

Inhibition of clastogenic effects of cesium chloride in mice in vivo by chlorophyllin

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 the mitogenicity and DNA aneuploid cell production, but could not counteract the combined effects of Areca and Nicotiana extracts. The experimental sets were characterised by gradual time-dependent production of DNA aneuploid cells, often between 4C and 6C range. The production of characteristic DNA aneuploid cells and DNA aneuploid spread of mode in the experimental sets along with mitogenicity of A. catechunuteindP. betle leaf and strong clastogenicity of N. tabacum point to the cytotoxic potential of the betel quid ingredients and the risk involved with its chewing.

International Journal of Pharmacognosy

Betel cytotoxicity: Further evidence from mouse bone marrow cells

The Histopathological Effect Of Chewing Of Betel Quid Without Tobacco Was Studied By Simulating 14 Different Chewing Habits Using The Mouse Glandular Stomach Mucosa As A Model Mammalian System. Chronic Oral Administration For 8 To 10 Months Resulted In Marked Architectural Atypia In Animals Receiving Extracts Of Areca Catechu L. Red Nut, With Piper Betle L. Varieties and A Combination Of Nut, Leaf and Lime. The Initial Histologic Changes Were Erosions and Regenerative Hyperplasia Of The Pyloric Glands. After Atrophy and Erosion Of The Mucosa, Regenerative Glandular Hyperplasia Developed In Animals Receiving Lime Suspension While Marked Adenomatous Hyperplasia Exhibiting Excessive Glandular Proliferation, Often With Peripheral Growth Into The Stomach Cavity, With Few Cellular Atypism Developed In Animals Receiving Combinations Of P. Betle Var. Bangla, A. Catechu and Low Concentration Of Lime (B Bn Lmn) and A. Catechu With Low Concentration Of Lime (Cbn Lmn). High Dose Of Lime Together With P. Betle L.Var. Bangla Probably Played A Protectant Role By Reducing The Dysplastic Changes and Metaplasia. The Leaf Var. Bangla Alone Was Found To Be An Irritant and Increased The Mitotic Index. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Sequential histologic alterations of mouse gastric mucosa following long-term simulation of betel addiction

Asia-Pacific Journal of Clinical Oncology

Issue Information

Food and Chemical Toxicology

IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 37. Tobacco habits other than smoking; Betel-quid and Areca-nut chewing; and some related nitrosamines

Journal	Pharmaceutical Biology
Publisher	Informa Healthcare
ISSN	1388-0209