Smoking and Smokeless Tobacco-Associated Human Buccal Cell Mutations and Their Association with Oral Cancer—A Review

Abstract

Reported herein are the results of a structured literature review that was undertaken to (a) determine if human buccal (mouth) cell changes are associated with smoking and smokeless (''chewing'') tobacco, (b) tabulate different buccal cell alterations that have been reported, (c) delineate buccal cell assays that have been used successfully, (d) determine whether buccal cell changes correlate with oral cancer as defined in clinicopathologic investigations, and (e) assess the feasibility of developing a high-throughput buccal cell assay for screening smokers for the early detection of oral cancer. The results of the studies reported herein have established that diverse buccal cell changes are associated with smoking and smokeless tobacco. This review documents also that buccal cells have been collected in a noninvasive manner, and repetitively for serial studies, from different sites of the mouth (e.g., cheek, gum, and tongue) and from normal tissue, preneoplastic lesions (leukoplakia), and malignant tumors. Tobacco-associated genetic mutations and nongenetic changes have been reported; a partial listing includes (a) micronuclei, (b) bacterial adherence, (c) genetic mutations, (d) DNA polymorphisms, (d) carcinogen-DNA adducts, and (e) chromosomal abnormalities. Clinical studies have correlated buccal cell changes with malignant tumors, and some oral oncologists have reported that the buccal cell changes are practical biomarkers. Summarily, the literature has established that buccal cells are useful not only for characterizing the molecular mechanisms underlying tobacco-associated oral cancers but also as exfoliative cells that express diverse changes that offer promise as candidate biomarkers for the early detection of oral cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1061 -77)

Self-perceived oral health status and cytomorphological changes in individuals with addictive oral habits: assessed by WHO oral health questionnaire for adults

“…The figure of micronuclei is identified to increase with carcinogenic stimuli. 40 Buccal cells micronuclei were more numerous between cigarette smokers as shown by previous studies. 41,42 Wu et al stated that buccal cell micronuclei were positively linked among micronuclei frequency and each cumulative smoking (packs/year) or smoking intensity (e.g., daily cigarette consumption).…”

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

“…Currently, the only useful measures to predict an individual's risk for developing lung or head and neck cancer are based on exposure, age of the individual and, if detectable, the presence of premalignant lesions. Given the significant role of carcinogen exposure in these tumours, it proves difficult to study host factors related to cancer risk (Proia et al, 2006). Such studies are based on measurement of host DNA repair capacity, such as the bleomycin chromosome breakage assay (Wu et al, 1998;Rajaee-Behbahani et al, 2001), the host-cell reactivation assay (Diem and Runger, 1997), or the comet assay (Kleinsasser et al, 2000).…”

Comparative Evaluation of Micronuclei in Exfoliated Urothelial Cells in Patients with Smoking and Smokeless Tobacco-associated Lesions: A Prospective Quantitative Study

“…In India, tobacco is commercially available in bidi, cigarette, cigar smoking tobacco forms, or gutkha, mawa, mishri, admixed with arecanut and slaked limesmokeless tobacco forms. 4,5 Benzo[a]pyrene and other polycyclic aromatic carcinogens are the most important carcinogenic agents in smoke, while unburnt tobacco contains 28 carcinogens of which the most harmful are the tobacco specific nitrosamines (TSNAs). The metabolites of nitrosamines, such as carcinogenic TSNAs N'-nitrosonornicotine (NNN), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosoanabasine as well as the volatile nitrosamines N-nitrosodimethylamine and N-nitrododiethylamine, have been detected in saliva of tobacco chewers.…”

“…The metabolites of nitrosamines, such as carcinogenic TSNAs N'-nitrosonornicotine (NNN), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosoanabasine as well as the volatile nitrosamines N-nitrosodimethylamine and N-nitrododiethylamine, have been detected in saliva of tobacco chewers. [4][5][6] Other cancer causing substances include formaldehyde, acetaldehyde, cortonaldehyde, hydrazine, arsenic, nickel, cadmium and benzopyrene. 6 Tobacco smoke contains more than 60 carcinogenic combustion products.…”

“…In particular, NNN, NNK and polycyclic aromatic hydrocarbons have been linked with genotoxi city. 5 Nitrosamines are also produced by the alkaloids in arecanut which are also carcinogenic. These agents are known to cause adverse effects at a cellular level, either directly at the site of placement or by indirect systemic effects.…”