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. 1992 Apr;118(4):283–288. doi: 10.1007/BF01208617

In vitro genotoxic effects of areca nut extract and arecoline

Bhavana J Dave 1, Amit H Trivedi 1, Siddharth G Adhvaryu 1
PMCID: PMC12201074  PMID: 1577847

Abstract

The genotoxic potential of the aqueous extract of areca nut as well as arecoline, the major alkaloid of the areca nut, was tested with the help of cytogenetic markers such as sister-chromatid exchanges and chromosome aberrations, utilizing Chinese hamster ovary (CHO) cells. The continuous-treatment and pulse-treatment schedules yielded dose-dependent elevations in the frequencies of sister-chromatid exchange and chromosomal aberration in CHO cells, indicating a genotoxic effect of both the extract and arecoline. The results also imply that, besides arecoline, there may be some other water-extractable substances in the areca nut that make the extract more genotoxic. The chromosome damage was found to be more severe on treating the cells with low concentrations and for longer duration, which mimic the effects of chronic areca nut consumption.

Key Words: Areca nut, Arecoline, Sister chromatid exchange, Chromosome aberrations, Genotoxicity

Abbreviations

SCE

sister-chromatid exchange

CA

chromosome aberration

CHO

Chinese hamster ovary

References

  1. Adhvaryu SG, Trivedi AH, Jani KH, Vyas RC, Dave BJ (1986) Genotoxic effects of ketamine on CHO cells. Arch Toxicol 59:124–125 [DOI] [PubMed] [Google Scholar]
  2. Ashby J, Styles JA, Boyland E (1979) Betel nuts, Arecaidine and oral cancer. Lancet 1:112 [DOI] [PubMed] [Google Scholar]
  3. Bhide SV, Shivapurkar NM, Gothoskar SV, Ranadive KJ (1979) Carcinogenicity of betel quid ingredients: feeding mice with aqueous extract and the polyphenol fraction of betel nut. Br J Cancer 40:922–926 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gupta PC, Pindborg JJ, Mehta FS (1982) Comparison of carcinogenicity of betel quid with and without tobacco: an epidemiological review. Ecol Dis 1:213–219 [PubMed] [Google Scholar]
  5. IARC (1985) 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. International Agency for Research on Cancer, Lyon [PubMed] [Google Scholar]
  6. Mathew AG, Venkataramu SD, Govindarajan VS (1964) Studies on areca nut, part 1. Changes in chemical composition and physical characteristics of nuts with maturity. Indian J Technol 2:90–96 [Google Scholar]
  7. Nair J, Ohshima HC, Freisen M, Croisy A, Bhide SV, Bartsch H (1985) Tobacco specific and betel nut specificN-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid. Carcinogenesis 6:295–303 [DOI] [PubMed] [Google Scholar]
  8. Natarajan AT, Obe G (1982) Mutagenicity testing with cultured mammalian cells: cytogenetic assays. In: Heddle JA (ed) Mutagenicity: new horizons in genetic toxicology. Academic Press, New York, pp 171–213 [Google Scholar]
  9. Panigrahi GB, Rao AR (1982) Chromosome-breaking ability of arecoline, a major betel-nut alkaloid, in mouse bone-marrow cells in vivo. Mutat Res 122:347–353 [DOI] [PubMed] [Google Scholar]
  10. Panigrahi GB, Rao AR (1986) Study of the genotoxicity of the total aqueous extract of betel nut and its tannin. Carcinogenesis 7:37–39 [DOI] [PubMed] [Google Scholar]
  11. Ranadive KJ, Ranadive SN, Shivapurkar NM, Gothoskar SV (1979) Betel quid chewing and oral cancer: experimental studies on hamsters. Int J Cancer 24:835–843 [DOI] [PubMed] [Google Scholar]
  12. Rao AR, Das P (1989) Evaluation of the carcinogenicity of different preparations of areca nut in mice. Int J Cancer 43:728–732 [DOI] [PubMed] [Google Scholar]
  13. Sankarnarayanan M, Mohindeen N, Krishnan Nair M, Padmanabhan TK (1989) Aetiology of oral cancer in patients>30 years of age. Br J Cancer 59:439–440 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Scott D (1980) Molecular mechanisms of chromosome structural changes. Toxicol Environ Sci 7:101–113 [Google Scholar]
  15. Shirname LP, Menon MM, Nair J, Bhide SV (1983) Correlation of mutagenicity and tumorigencity of betel quid and its ingredients. Nutr Cancer 5:87–91 [DOI] [PubMed] [Google Scholar]
  16. Shirname LP, Menon MM, Bhide SV (1984) Mutagenicity of betel quid and its ingredients using mammalian test systems. Carcinogenesis 5:501–503 [DOI] [PubMed] [Google Scholar]
  17. Shivapurkar NM, Ranadive SN, Gothoskar SV, Bhide SV, Ranadive KJ (1980) Tumorigenic effect of aqueous and polyphenolic fractions of betel nut in Swiss strain mice. Indian J Exp Biol 18:1159–1161 [PubMed] [Google Scholar]
  18. Shivshankar S, Dhanaraj S, Mathew AG, Srinivasa Murthy S, Vyasamurthy MN, Govindarajan VS (1969) Physical and chemical characteristics of processed areca-nuts. J Food Sci Technol 41:113–116 [Google Scholar]
  19. Silverberg E, Lubera JA (1989) Cancer Statistics. CA 39:3–20 [DOI] [PubMed] [Google Scholar]
  20. Sinha A, Rao AR (1985) Induction of shape abnormality and unscheduled DNA synthesis by arecoline in the germ cells of mice. Mutat Res 158:189–192 [DOI] [PubMed] [Google Scholar]
  21. Stich HF, Tsang SS (1989) Promoting activity of betel quid ingredients and their inhibition by retinol. Cancer Lett 45:71–77 [DOI] [PubMed] [Google Scholar]
  22. Stich HF, Stich W, Lam PPS (1981) Potentiation of genotoxicity by concurrent application of compounds found in betel quid: arecoline, eugenol, quercetin, chlorogenic acid and Mn2+. Mutat Res 90:355–363 [DOI] [PubMed] [Google Scholar]
  23. Stich HF, Bohm BA, Chaterjee K, Sailo J (1983) The role of saliva borne mutagens and carcinogens in the etiology of oral and esophageal carcinomas of betel nut and tobacco chewers. In: Stich HF (ed) Carcinogens and mutagens in the environment, vol 3. Naturally occurring compounds: epidemiology and distribution. CRC Press, Boca Raton, pp 43–58 [Google Scholar]
  24. Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafstrom RC (1989) Cytotoxic and genotoxic effects of areca nut related compounds in cultured human buccal epithelial cells. Cancer Res 49:5294–5298 [PubMed] [Google Scholar]
  25. Umezawa K, Fujie S, Sawamura M, Matsushima T, Katoh Y, Tanaka M, Takayama S (1981) Morphological transformation, sister chromatid exchange and mutagenesis assay of betel constituents. Toxicol Lett 8:17–22 [DOI] [PubMed] [Google Scholar]
  26. Wary KK, Sharan RN (1988) Aqueous extract of betel-nut of North-East India induces DNA strand breaks and enhances rate of cell proliferation in vitro. J Cancer Res Clin Oncol 114:579–582 [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wary KK, Sharan RN (1991) Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro. Int J Cancer 47:396–400 [DOI] [PubMed] [Google Scholar]
  28. WHO (1984) Control of oral cancer in developing countries. Bull WHO 62:817–830 [PMC free article] [PubMed] [Google Scholar]
  29. WHO (1985) Guide to short-term tests for detecting mutagenic and carcinogenic chemicals. Environmental Health Criteria 51. World Health Organization, Geneva, pp 57–67 [Google Scholar]

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