title: Smokeless tobacco (paanandgutkha) consumption, prevalence, and contribution to oral cancer.
abstract: Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such aspaanandgutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing ofpaanand swallowing ofgutkhatrigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used inpaanandgutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kamal
authors.identifier: 0000-0001-8670-4356
authors.initials: K
authors.lastname: Niaz
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Faheem
authors.identifier: 0000-0001-7728-664X
authors.initials: F
authors.lastname: Maqbool
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fazlullah
authors.identifier: 0000-0003-2473-6090
authors.initials: F
authors.lastname: Khan
authors.affiliation: Institute of Paramedical Sciences, Khyber Medical University, Peshawar, Pakistan.
authors.forename: Haji
authors.identifier: 0000-0003-2458-5843
authors.initials: H
authors.lastname: Bahadar
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatima
authors.identifier: 0000-0003-1250-0048
authors.initials: F
authors.lastname: Ismail Hassan
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.identifier: 0000-00030123-1209
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D001208:Asia / Q000453:epidemiology; D004249:DNA Damage; D005260:Female; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000453:epidemiology*; D009602:Nitrosamines / Q000506:poisoning*; D009914:Oral Submucous Fibrosis / Q000139:chemically induced / Q000453:epidemiology*; D015995:Prevalence; D012727:Sex Characteristics; D013636:Tanzania / Q000453:epidemiology; D014030:Tobacco, Smokeless / Q000009:adverse effects / Q000706:statistics & numerical data*
chemical_list: D009602:Nitrosamines
keywords: Areca; Fibrosis; Oral cancer; Prevalence; Smokeless tobacco