Localized formation of micronuclei in the oral mucosa and tobacco-specific nitrosamines in the saliva of "reverse" smokers, Khaini-tobacco chewers and gudakhu users.

"Reverse"-cigar smokers (who hold the burning end of cigars within the mouth), dippers (who place a mixture of Khaini-tobacco and slaked lime into the lower gingival groove) and users of tobacco-containing toothpaste (gudakhu) in Orissa, India, were examined for precancerous oral lesions, the frequency of micronucleated cells at 3 different intra-oral sites, and levels of tobacco-specific nitrosamines (TSNA) in the saliva. Among reverse-cigar smokers, a high incidence of leukokeratosis nicotina palati, an elevated frequency of micronucleated cells in the palate (2.5% as compared to 0.6% in non-smokers and non-chewers of tobacco) and tongue (2.1%) from which carcinomas preferentially develop, and up to 5890 ppb nitrosonornicotine and up to 1880 ppb N-nitrosoanatabine in the saliva were found. Among Khaini-tobacco chewers, the frequency of micronucleated cells was elevated to 2.1% in the gingival groove, and up to 1580 ng N-nitrosonornicotine, 690 ng N-nitrosoanatabine, 90 ng N-nitrosoanabasine, and 180 ng 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone) per ml of saliva were observed. The localized elevation of the frequency of micronuclei and cancer development is probably due to a synergistic effect of hyperthermia and tobacco-related carcinogens among reverse-cigar smokers, and to the close, prolonged contact between the mucosa and tobacco among Khaini-tobacco/slaked lime dippers. Neither pre-cancerous lesions nor an elevated frequency of micronuclei were seen in the oral mucosa of users of gudakhu, a tobacco-containing toothpaste, which may be due to the low amount of TSNA released from the gudakhu and the short exposure time, which is restricted to the period of tooth brushing.