The Effects of Betel-Nut Chewing on the Buccal Mucosa: A Histological Study

Abstract

SUMMARY.-Sixty-two " leukoplakias " from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from nontobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacco-containing quids were chewed as compared to non-tobacco-containing quids.An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the " intensity " of the habit.THE clinical effects of betel-nut chewing on the buccal mucosa of a sample of 296 Malaysians have been reported in a separate paper (Chin and Lee, 1970). The present paper deals with the histological changes seen in the buccal mucosa of chewers from this sample whose oral mucosa exhibited lesions conforming to the clinical appearance of " leukoplakia " as defined previously. Pindborg, Srivastava and Gupta (1964) described epithelial changes in tobacco-induced leukoplakias in India and referred to previous work on this aspect. They pointed out that previous workers have not correlated histological findings with different habits and have not analysed the type of keratinization in these lesions. They concluded from their pilot study of 39 biopsies from leukoplakias in 37 East Indians that various habits of tobacco consumption, although creating a similar clinical picture of leukoplakia cause microscopically different changes of the oral epithelium and that the oral epithelium may react differently in different locations.Sirsat and Doctor (1967) studied the effects of tobacco chewing on the buccal mucosa in Indians with and without oral carcinomas and concluded that hyperplasia of the epithelium was the commonest change observed among chewers, and that parakeratosis was also a common finding, whereas hyperkeratosis was less commonly observed.

Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells

“…Development of resistance to terminal differentiation stimuli is a key event in carcinogenesis, as evident from experimental data (Cerutti, 1988;Harris, 1991) and from abnormal differentiation patterns in human tumors, including those of oral origin (Eisenberg et a/., 1987). Betel quid chewing is also associated with abnormal differentiation patterns, as demonstrated by the common findings of hyperkeratosis, hyperplasia and acanthosis (Reichart et al, 1984;Tennekoon and Bartlett, 1969;Lee and Chin, 1970). In this study, an increase in involucrin expression was found after exposure to the extract in normal buccal epithelial cells, but not in SqCCiYl cells, which are also resistant to endogenous differentiationinducing agents (Sundqvist eta/., 1 9 9 1~) .…”

“…Betel quid chewing is also associated with abnormal differentiation patterns, as demonstrated by the common findings of hyperkeratosis, hyperplasia and acanthosis (Reichart et al, 1984;Tennekoon and Bartlett, 1969;Lee and Chin, 1970). In this study, an increase in involucrin expression was found after exposure to the extract in normal buccal epithelial cells, but not in SqCCiYl cells, which are also resistant to endogenous differentiationinducing agents (Sundqvist eta/., 1 9 9 1~) .…”

“…Such effects would result in continued exposure of the cells to the extract in the growth assay, although it involves delicate rinsing of the cells after exposure, and change of medium during the growth period. This is in accordance with reports that betel chewers have betel mixture incrustations on the oral mucosal surface (Reichart et a/., 1984;Lee and Chin, 1970), and analysis by transmission electron microscopy of the mucosa shows crystalloid aggregations in the intercellular spaces in suprabasal layers, probably derived from the quid A (Reichart et al, 1984). Areca-nut alkaloids may be involved in this effect, since granular deposits are found on the oral mucosal epithelium in rats exposed by topical application of the major alkaloid of areca nut, arecoline (Sirsat and Khanolkar, 1962).…”

“…The high frequency of oral cancers in Asia is linked to the chewing of betel quid, which is a common habit in that part of the world (IARC, 1985). Betel quid chewing is also associated with other pathological states of the oral epithelia, such as disturbed differentiation and incrustations of betel-quidderived material (Reichart et al, 1984;Lee and Chin, 1970). Of thc major ingredients of the quid, tobacco is clearly linked to human cancer.…”

Changes in vitamin A conditioned hamster cheek pouch epithelium on exposure to commercial shell lime (calcium hydroxide) and tobacco I — Optical histopathology

“…As seen in Table 2, all but two vitamin A controls show hyperorthokeratosis and only two show parakeratosis. In both rodent and human epithelium, keratinizalion occurs in response to trauma, be it inflicted artificially (Dunham & Herrold 1962, Dunham et al 1966, Sirsat & Kandarkar 1968 or in the course of addictive exposure to the ingredients of the betel chew (Sirsat & Doctor 1967, Lee & Chin 1970, Sirsat et al 1974. This marked provocation of anomalous keratinization by the test substances makes it difficult to judge effectively the role of superimposed vitamin A on the enhancement of this epithelial morbidity.…”