A study of betel quid carcinogenesis. II. Formation of N-nitrosamines during betel quid chewing.
In model studies, nitrosation of the major areca alkaloid, arecoline, leads to the formation of N-nitrosoguvacoline, 3-(methylnitrosamino)propionitrile (MNPN), 3-(methylnitrosamino)propionaldehyde and two unknown N-nitrosamines. MNPN is a strong carcinogen in Fischer 344 rats. After subcutaneous injection of 1.1 mmol MNPN in 60 doses, all 15 male and 15 female rats developed tumours within 24 weeks; multiple tumours occurred in 26 of the rats. Eighty-seven percent of the animals had tumours of the oesophagus, 70% had nasal cavity tumours, 37% had tumours of the tongue, 7% tumours of the pharynx and 7% tumors of the forestomach. At the dose used, male and female rats showed no significant difference in tumour incidence or site of tumours. The formation of MNPN during betel quid chewing, although likely, has not yet been proven, while the areca-derived N-nitrosamine, N-nitrosoguvacoline (NG), has been found in the saliva of betel quid chewers at levels of 2.2-348 micrograms/L. N-Nitrosoguvacoline levels were higher in the saliva of chewers who used betel quid together with tobacco. The saliva of these chewers also contained tobacco-specific N-nitrosamines.
D000818:Animals; D001114:Areca; D001115:Arecoline / Q000378:metabolism; D001681:Biological Assay; D002273:Carcinogens / Q000378:metabolism*; D006801:Humans; D008409:Mastication; D009602:Nitrosamines / Q000032:analysis / Q000378:metabolism*; D009603:Nitroso Compounds / Q000032:analysis / Q000378:metabolism; D010946:Plants, Medicinal; D051381:Rats; D011916:Rats, Inbred F344; D012463:Saliva / Q000032:analysis
D002273:Carcinogens; D009602:Nitrosamines; D009603:Nitroso Compounds; D001115:Arecoline; C036676:N-nitrosoguvacoline; C042162:3-(methylnitrosamino)propionitrile; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C032978:N'-nitrosoanatabine; C008655:N'-nitrosonornicotine