Carcinogenic tobacco-specific N-nitrosamines in US cigarettes: three decades of remarkable neglect by the tobacco industry.
ABSTRACT Modification of tobacco curing methods and other changes in cigarette manufacturing techniques could substantially reduce the levels of tobacco-specific nitrosamines (TSNA), a group of potent carcinogens, in cigarette smoke. In 1999, two major US cigarette manufacturers stated their intent to move towards using tobaccos low in TSNA. There is no information available on current TSNA levels in tobacco of various cigarettes available in the US, particularly in the newer varieties introduced over the past decade.
Seventeen brands of cigarettes were purchased in April of 2010 from retail stores in Minnesota. TSNA levels were measured in the tobacco filler and smoke of these cigarettes.
In all brands, the sum of two potent carcinogenic TSNA--4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine--in cigarette filler averaged 2.54 (± 1.05) μg/g tobacco. This value is virtually identical to the sum of these two carcinogens reported for the tobacco of a US filtered cigarette in 1979. TSNA levels in smoke positively correlated with those in tobacco filler of the same cigarettes.
We found no indication that any meaningful attempt was made to reduce or at least control TSNA levels in the new varieties of the popular brands Marlboro and Camel introduced over the last decade. In light of the recently granted regulatory authority to the FDA over tobacco products, regulation of TSNA levels in cigarette tobacco should be strongly considered to reduce the levels of these potent carcinogens in cigarette smoke.
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ABSTRACT: INTRODUCTION: N'-nitrosonornicotine (NNN), an esophageal and oral carcinogen present in tobacco products, has a chiral center in its structure. Of its two enantiomers, (S)-NNN exhibits higher tumorigenic potency than (R)-NNN. There is no information available on the levels of (S)-NNN in various tobacco products currently marketed in the United States. METHODS: We used chiral gas chromatography analysis to determine (S)-NNN levels in a convenience sample of 37 tobacco products currently marketed in the United States: conventional smokeless tobacco, novel smokeless tobacco products, and cigarette tobacco filler. RESULTS: Among all products analyzed here, (S)-NNN averaged 62.9±6.3% (SD) of NNN. The absolute amount of (S)-NNN in conventional moist snuff averaged 1.26±0.5 µg/g tobacco; in novel smokeless products 0.70±0.2 µg/g tobacco; and in cigarette filler 1.36±0.6 µg/g tobacco (all values are per wet weight). For each cigarette brand, the enantiomeric composition of NNN in cigarette smoke was similar to that of the corresponding tobacco filler. CONCLUSIONS: Our results demonstrate that (S)-NNN is the predominant NNN enantiomer in moist snuff, novel smokeless tobacco products, and cigarettes currently marketed in the United States. Efforts toward the reduction of NNN in U.S. tobacco products should take into account its enantiomeric composition, with particular focus on (S)-NNN as a causative agent for esophageal and oral cancers associated with tobacco use.Nicotine & Tobacco Research 12/2012; · 2.48 Impact Factor
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ABSTRACT: The WHO TobReg proposed mandating ceilings on selected smoke constituents determined from the market-specific median of nicotine-normalized yield distributions. Data validating this regulatory concept were obtained from essentially single-blend surveys. This process is strongly impacted by inverse correlations among yields. In the present study, 18 priority WHO smoke constituent yields (nicotine-normalized) were determined (using 2 smoking regimens) from 262 commercial brands including American, Virginia and local blends from 13 countries. Principal Component Analysis was used to identify yields patterns, clustering of blend types and the inverse correlations causing these clusters. Three principal components explain about 75% of total data variability. PC(1) was sensitive to the relative levels of gas- and particle-phase compounds. PC(2) and PC(3) cluster American- and Virginia-blends, revealing inverse correlations: Nitrogen oxides and amino- or nitroso-aromatic compounds inversely correlate to either formaldehyde and acrolein, or benzo(a)pyrene and di-hydroxybenzenes. These results can be explained by reviewing the processes determining each components smoke delivery. Regulatory initiatives simultaneously targeting selected smoke constituents in markets with mixed blend styles will be strongly impacted by the inverse correlations described. It is difficult to predict the ultimate impact of such regulations on public health, considering the complex chemistry of cigarette smoke formation.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 01/2013; · 2.99 Impact Factor
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ABSTRACT: The association of tobacco smoke with decreased cell motility and wound healing is well documented; however, the cellular mechanisms and specific toxic tobacco constituents responsible for this effect are not well understood. Tobacco-specific N-nitrosamines (TSNAs) are among the most important classes of carcinogens found in tobacco products. The TSNA N'-nitrosonornicotine (NNN) is present at relatively high levels in tobacco and its smoke, as well as second- and third-hand smoke. To investigate the cellular pathways that are perturbed upon NNN exposure, we employed a quantitative proteomic approach, utilizing stable isotope labeling by amino acids in cell culture and mass spectrometry, to assess the NNN-induced alteration of protein expression in GM00637 human skin fibroblast cells. With this approach, we were able to quantify 2599 proteins, 191 of which displayed significantly changed expression following NNN exposure. One of the main findings from our proteomic analysis was the down-regulation of six different subunits of myosin, particularly non-muscle myosin II heavy chain, isoforms A, B, and C. In addition, we found the altered expression of several extracellular matrix proteins and proteins involved in cellular adhesion. Together, our quantitative proteomic results suggested that NNN exposure may interfere with fibroblast motility. An in vitro scratch wound assay results supported that NNN exposure reduced the ability of dermal fibroblast to migrate into the scratched area. The results from the present study offered novel insights into the cellular mechanisms of NNN toxicity and identified NNN as a specific tobacco constituent that contributes to decreased fibroblast migration.Journal of Proteome Research 01/2013; · 5.06 Impact Factor