Comparison of tobacco-specific nitrosamine levels in smokeless tobacco products: High levels in products from Bangladesh

Abstract

Head and neck cancers are among the most common cancers in Southeast Asia and are likely to face sharp increases in the coming years due to the widespread use of smokeless tobacco (SLT) products. Bangladesh has the second highest oral cancer mortality rate as well as the second highest rate of SLT product usage worldwide. SLT products contain high levels of the highly carcinogenic tobacco‐specific nitrosamines (TSNAs); they include N‐nitrosonornicotine (NNN), 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), N‐nitrosoanatabine (NAT), and N‐nitrosoanabasine (NAB). To date, the amount of TSNAs present in Bangladeshi SLT products has not been reported. The goal of the present study was to develop an efficient TSNA and nicotine extraction method to quantify the levels of TSNAs and nicotine present in 31 Bangladeshi SLT products. The concentration of NNN, NNK, NAT, and NAB in Bangladeshi SLT brands ranged from 1.07–59.18 μg/g SLT, 0.15–33.70 μg/g SLT, 0.79–44.64 μg/g SLT, and 0.03–12.85 μg/g SLT, respectively. Pan Masala, which is labeled as a non‐tobacco product, also contains low levels of TSNAs. Betel nut, a common flavor additive in SLT products in Bangladesh, contained no detectible TSNA levels. Bangladeshi SLT products contained significantly higher (p<0.05) levels of TSNAs as compared to SLT brands from the United States (U.S.), and were higher on average than the levels observed in brands in other regions of southern Asia. NNN and NNK levels were 16 and 19, 2 and 3.5, and 62 and 85 fold higher than U.S., Indian and Pakistani SLT brands, respectively. Additionally, the levels of NNN and NNK measured in U.S. brands in this study were 1.2‐fold higher than previously reported values from 2013. This study demonstrates that the levels of TSNAs, including the major tobacco carcinogens NNN and NNK, are far higher in Bangladeshi SLT brands than they are in other regions of the world. Exposure to such high levels of carcinogens may be the most important contributing factor to the rate of head and neck as well as other tobacco‐related cancers observed in Bangladesh. Support or Funding Information This work is supported in part by grants from NIH, National Cancer Institute (grant R01‐ES025460, to P. Lazarus) and the Health Sciences and Services Authority of Spokane, Washington (grant WSU002292, to College of Pharmacy and Pharmaceutical Sciences, Washington State University) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Smokeless tobacco policy in Bangladesh: A stakeholder study of compatibility with the World Health Organization's Framework Convention on Tobacco Control

“…Most of the ST products available in World Health Organization (WHO) South-East Asia Regional Office countries are found to be carcinogenic, cardiotoxic, mutagenic and to contain heavy metals [7,14]. Recent studies found high levels of carcinogenic tobacco-specific nitrosamines in significant numbers of ST products in Bangladesh [1,15]. Despite high prevalence (20.6%) compared to the prevalence of smoking tobacco (18.0%) and negative health consequences, ST is less of a public health priority in Bangladesh due to perceived less harmful effects and social and cultural acceptance [16].…”

Composition and Ecological Functionality of Fungal Communities Associated with Smokeless Tobacco Products Mainly Consumed in India

“…TSNAs are the most abundant carcinogens in smokeless tobacco products (STPs) and can transform normal cells into cancerous cells ( 11 ). TSNA levels were found to be higher in STPs available in South-Asian countries than in those of Western countries ( 12 ). The levels of TSNAs in STPs depend upon tobacco constituents, moisture, temperature, pH, environmental conditions, storage conditions, curing processes, and aging of the products ( 12 – 19 ).…”

Structure‐based study to identify alkaloids as promising cytochrome P450 (CYP1A1) inhibitors: An in silico approach using virtual screening, molecular dynamic simulations, and binding free energy calculation

“…15 SLT contains several carcinogens like TSNAs including N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N′-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3pyridyl)-1-butanol (NNAL), N′-nitrosoanatabine (NAT), PAHs, N-nitrosamine acids, and many others. 16,17 Chemically, CYP450 reacts with toxic substances present in SLT products to produce reactive intermediates that can damage DNA. 18 During the reaction mechanism of carcinogenesis, NNK reduces to NNAL, CYP-450 reacts with NNAL to form alpha hydroxyl NNAL that produces diazonium ions and aldehydes due to its instability and upon interaction with DNA to form DNA adducts.…”

“…The noncombustible forms of tobacco (smokeless tobacco [SLT] products) are popularly consumed in India and attributed to oral carcinogenesis 15 . SLT contains several carcinogens like TSNAs including N′‐nitrosonornicotine (NNN), 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), N′‐nitrosoanabasine (NAB), 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL), N′‐nitrosoanatabine (NAT), PAHs, N ‐nitrosamine acids, and many others 16,17 . Chemically, CYP450 reacts with toxic substances present in SLT products to produce reactive intermediates that can damage DNA 18 .…”