Aqueous extract of betel-nut of North-East India induces DNA-strand breaks and enhances rate of cell proliferation in vitro

Wary, Kishore K.; Sharan, R.N.

doi:10.1007/bf00398180

Cited by 60 publications

(41 citation statements)

References 12 publications

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“…In such a situation, NaNO, and arecoline probably react with each other to produce several NOCs of arecoline which are capable of interacting with the nucleophilic sites of DNA. This interaction could explain our present observations as well as our earlier observation of DNA strand breaks (Wary and Sharan, 1988) or induction of cross-links within DNA, or between DNA and proteins (IARC, 1985). We conclude that arecoline and NaNO, are intensely cytotoxic and cytostatic when administered together in the presence of S-9 at PH 4.2.…”

Section: Discussionsupporting

confidence: 58%

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Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro

Wary

Sharan

1991

Intl Journal of Cancer

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Arecoline, an active alkaloid of Areca catechu L., and sodium nitrite, a food additive, are highly cytotoxic and cytostatic on the Hep 2 cell line when administered in an acidic environment (pH 4.2) in the presence of S-9 mixture. Hep 2 cells (10(6)) were treated with either 0.145, 0.725 or 1.449 mM sodium nitrite or 0.042, 0.085 or 0.339 mM arecoline or sodium nitrite (0.145 mM) plus varied concentrations of arecoline (0.042, 0.085 or 0.339 mM). Their effects were additive in nature. Hep 2 cells exposed to this combination showed reduced cell survival, and lower rates of DNA and protein syntheses. Involvement of N-nitroso derivatives of arecoline is suggested to explain the results. On the basis of these studies, we speculate that N-nitroso compounds derived from arecoline can (weakly) interact with DNA.

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Section: Discussionsupporting

confidence: 58%

“…We have shown that arecoline is toxic to kidney cells in vitro (Wary and Sharan, 1988). In the present investigation we find that the toxicity of arecoline is apparently enhanced due to the presence of NaNO, in an acidic environment.…”

Section: Discussionmentioning

confidence: 56%

Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro

Wary

Sharan

1991

Intl Journal of Cancer

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“…In addition mating began 2 weeks after completion of test feeding and second F1 litters contained diabetic offspring from Group 2 betel-fed adults, as reported with other nitrosamine-induced diabetes [19]. The major abnormalities reported in the heads of spermatozoa 30 days after completion of 5 days administration of pan masala (a betel-nut containing snack) to adult mice [20], and the damage to chromosomes in circulating lymphocytes in man and mouse following betel consumption suggests a nuclear mutation should be considered [21], though the more rapid rates of mitochondrial mutation would provide a mechanism for the marked changes in disease incidence between generations [22]. Epidemiological studies of risk markers for diabetes in relation to dietary factors including betel chewing carried out in East London are being analysed in relation to glycaemia (B. J. Boucher, N. Mannan, unpublished observations).…”

Section: Discussionmentioning

confidence: 81%

Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring

1994

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SummaryMany mutagenic nitroso compounds are also diabetogenic. Betel-nut (Areca catechu) chewing populations have an increased incidence of foregut cancers related to betel-nut nitrosamines which suggests that betel consumption could be diabetogenic. Young adult CD1 mice with a low spontaneous incidence of diabetes were fed betel nut in standard feed for 2~5 days. Single point (90 min) intra-peritoneal glucose tolerance tests were used to follow glucose tolerance up to 6 months of age. Glucose intolerance was defined as over 3 SD above mean control values. Glucose intolerance was found in 3 of 51 male and 4 of 33 female adult mice which were fed the betel diet (p < 0.01). Studies on the progeny of these mice are presented separately for animals studied in Aberdeen (Group 1) and London (Group2). In matings of Group 1 betel-fed parents glucose intolerance was found in 4 of 25 male and 1 of 22 female F1 offspring, with significant hyperglycaemia in F1 males born to hyperglycaemic but not to normoglycaemic mothers (p < 0.01). In the F2 generation 4 of 23 males and 1 of 16 females and in the F3 generation 1 of 16 males and 0 of 20 females were glucose intolerant. In the Group 2 studies where betel-fed parents were mated to normal controls glucose intolerance was found in 10 of 35 male and 10 of 33 female F1 progeny (p < 0.005), and mean islet areas were increased in offspring of betel-fed parents (p < 0.001). The total incidence of glucose intolerance in F1 progeny from studies in Groups 1 and 2 was 14 of 60 males and 11 of 55 females (p < 0.005). Insulin dependence did not develop in the glucose-intolerant betel-fed animals or their descendants; affected animals appearing well built and active. The development of glucose intolerance in F1 offspring was not dependent on maternal glucose intolerance or on maternal betel-feeding, and 90-min glucose levels of F1 offspring were directly related to paternal but not to maternal glycaemia (p < 0.01). Our findings suggest that betelnut (Areca) consumption may be diabetogenic and induce an inheritable abnormality. The hypothesis is of interest in view of the widespread habit of betel consumption and of the strategies known to inhibit the induction of experimental diabetes by diabetogenic nitroso compounds. [Diabetologia (1994) 37: 49-55]

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“…At cellular and molecular levels, BN extract was found to decrease the cell survival, vital dye accumulation, and membrane integrity of cultured human buccal epithelial cells and to induce formation of both DNA single strand breaks and DNA-protein cross links (Sundqvist et al, 1989). Ripe BN extract induced significant decline in population doubling, increase in senescence, cell-cycle arrest at G 1 /S phase, and decrease in cell proliferation of cultured normal human oral keratinocytes (Lu et al, 2006), and an aqueous extract of BN (AEBN) induced DNA-strand breaks and enhanced cell proliferation of mouse kidney cells in vitro (Wary and Sharan, 1988). Exposure of Swiss Albino mice to AEBN has also been reported to induce formation of preneoplastic nodules of the liver (Sharan, 1996).…”

Section: Introductionmentioning

confidence: 98%

Ultrastructural alterations in liver of mice exposed chronically and transgenerationally to aqueous extract of betel nut: Implications in betel nut‐induced carcinogenesis

Choudhury

Sharan

2009

Microscopy Res & Technique

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The aqueous extract of betel nut (AEBN) induces the formation of preneoplastic nodules in the liver of Swiss Albino mice and leads to increased predisposition to cancer when administered transgenerationally. The aim of this investigation was to elucidate the alterations in ultrastructure of subcellular organelles in the liver nodules using transmission electron microscopy and to determine whether these alterations have implications in AEBN-induced carcinogenesis. Male and female Swiss Albino mice were exposed to AEBN chronically and transgenerationally at a dose of 2 mg/mL in drinking water for 24 weeks. Extensive polymorphism was noted in nuclear shape and heterochromatin organization. Heterochromatin aggregation and marginalization were observed in the nuclei of chronically exposed mice, whereas transgenerationally exposed mice exhibited dispersion or loss of heterochromatin. The nuclear envelope was disrupted, and the nucleoli were enlarged in chronically exposed mice, whereas in transgenerationally exposed mice the nucleoli were reduced in size or totally absent. The cisternae of the rough endoplasmic reticulum were dilated and disrupted, and a large number of autophagic vesicles were observed in both chronically and transgenerationally exposed mice. Atypical mitochondria that underwent extensive cristolysis and progressively declined in size and number from the chronically exposed mice to the different generations of transgenerationally exposed mice were also observed. Thus, exposure to AEBN resulted in severe loss of ultrastructural integrity of cells in the liver nodules, and the progressive loss of mitochondrial function appeared to play a significant role in increasing the predisposition to cancer of mice exposed transgenerationally to AEBN.

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Aqueous extract of betel-nut of North-East India induces DNA-strand breaks and enhances rate of cell proliferation in vitro

Cited by 60 publications

References 12 publications

Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro

Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro

Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring

Ultrastructural alterations in liver of mice exposed chronically and transgenerationally to aqueous extract of betel nut: Implications in betel nut‐induced carcinogenesis

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