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High fructose diets are associated with an increased risk of liver cancer. Previous studies in mice suggest increased lipogenesis is a key mechanism linking high fructose diets to liver tumour growth. However, these studies administered fructose to mice at supraphysiological levels. The aim of this study was to determine whether liver tumour growth and lipogenesis were altered in mice fed fructose at physiological levels. To test this, we injected male C57BL/6 mice with the liver carcinogen diethylnitrosamine and then fed them diets without fructose or fructose ranging from 10 to 20 % total calories. Results showed mice fed diets with ≥15 % fructose had significantly increased liver tumour numbers (2-4-fold) and total tumour burden (∼7-fold) vs mice fed no-fructose diets. However, fructose-associated tumour burden was not associated with lipogenesis. Conversely, unbiased metabolomic analyses revealed bile acids were elevated in the sera of mice fed a 15 % fructose diet vs mice fed a no-fructose diet. Using a syngeneic ectopic liver tumour model, we show that ursodeoxycholic acid, which decreases systemic bile acids, significantly reduced liver tumour growth in mice fed the 15 % fructose diet but not mice fed a no-fructose diet. These results point to a novel role for systemic bile acids in mediating liver tumour growth associated with a high fructose diet. Overall, our study shows fructose intake at or above normal human consumption (≥15 %) is associated with increased liver tumour numbers and growth and that modulating systemic bile acids inhibits fructose-associated liver tumour growth in mice., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Correlations are made between mainstream cigarette smoke deliveries of individual PAHs over multiple years. Average overall PAH deliveries in mainstream cigarette smoke by study year, mentholation, ring size, and manufacturer are compared., Methods: Mainstream smoke deliveries were determined by GC/MS for 14 polycyclic aromatic hydrocarbons (PAHs) from selected cigarettes on the US market in 2002, 2004, 2007, and 2011. The mainstream smoke PAH emissions were measured under international standardization organization (ISO) smoking conditions. Pearson product-moment correlation was used to examine the linear relationship among the PAHs over multiple years., Results: A number of the PAH analytes were statistically highly correlated with each other. The overall average for mainstream smoke deliveries of PAHs did not change significantly between study years. Similar levels in average PAH deliveries were seen for mentholated and non-mentholated cigarettes., Conclusions: The strong correlations between PAH compounds over multiple years show that a limited set of PAHs can predict deliveries of others with confidence over multiple years. A more limited panel of analytes may be considered when designing studies involving PAH measurements in mainstream smoke., Competing Interests: Conflict of Interest Statement None.

Introduction: We developed a high throughput method for estimating smoker's mainstream smoke intake on a per-cigarette basis by analyzing discarded cigarette butts. This new method utilizes ultraviolet/visible (UV-Vis) spectrophotometric analysis of isopropanol-soluble smoke particulate matter extracted from discarded cigarette filters., Methods: When measured under a wide range of smoking conditions for a given brand variant, smoking machine delivery of nicotine, benzene, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines can be related to the overall filter extract absorbance at 360 nm. Once this relationship has been established, UV-Vis analysis of a discarded cigarette filter butt gives a quantitative measure of a smoker's exposure to these analytes., Results: The measured mainstream smoke constituents correlated closely (correlation coefficients from 0.9303 to 0.9941) with the filter extract absorbance. These high correlations held over a wide range of smoking conditions for 2R4F research cigarettes as well as popular domestic cigarette brands sold in the United States., Conclusions: This low cost, high throughput method is suitable for high volume analyses (hundreds of samples per day) because UV-Vis spectrophotometry, rather than mass spectrometry, is used for the cigarette filter butt analysis. This method provides a stable and noninvasive means for estimating mouth-level delivery of many mainstream smoke constituents. The ability to gauge the mouth-level intake of harmful chemicals and total mainstream smoke for cigarette smokers in a natural setting on a cigarette-by-cigarette basis can provide insights on factors contributing to morbidity and mortality from cigarette smoking, as well as insights on strategies related to smoking cessation., (Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Iq'mik, a form of smokeless tobacco (ST), is traditionally used by Cup'ik and Yup'ik Eskimo people of western Alaska. Iq'mik is sometimes incorrectly considered to be a healthier alternative to smoking because its ingredients are perceived as "natural." Our chemical characterization of iq'mik shows that iq'mik is not a safe alternative to smoking or other ST use., Methods: We measured nicotine and pH levels of tobacco and ash used to prepare iq'mik. We also characterized levels of toxins which are known to be present in ST including tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) using chromatographic separations coupled with isotope dilution mass spectrometry., Results: Nicotine content in the iq'mik tobacco was very high, ranging from 35 to 43 mg/g, with a mean of 39 mg/g. The pH of the iq'mik tobacco-ash mixture was 11, an extremely high level compared with most ST products. High levels of PAHs were seen in the fire-cured tobacco samples with a benzo[a]pyrene level of 87 ng/g. Average TSNA levels in the tobacco were 34, 2,700, and 340 ng/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively., Conclusions: Iq'mik contains high levels of the more easily absorbed unionized nicotine as well as known carcinogenic TSNAs and PAHs. The perception that iq'mik is less hazardous than other tobacco products due to the use of "natural" ingredients is not warranted. This chemical characterization of iq'mik gives a better understanding of the risk of possible adverse health effects of its use.

Background: It has been reported that charcoal added to cigarette filters selectively removes many of the more volatile chemicals, but it is not clear to what extent charcoal may reduce the delivery of important less volatile chemical constituents in mainstream cigarette smoke., Methods: We analysed machine-derived mainstream smoke deliveries (under three smoking regimens) for variants of a charcoal-filtered cigarette commercially test-marketed in the USA, focusing on selected polycyclic aromatic hydrocarbons (PAHs), phenols and tobacco-specific nitrosamines (TSNAs)., Results: While charcoal-containing filters selectively removed lower molecular weight PAHs from mainstream smoke, they did not significantly remove the heavier and more toxic PAHs studied, such as benzo[a]pyrene, a known carcinogen. Likewise, charcoal-containing filters removed phenols and TSNAs from mainstream smoke to differing amounts depending on the compound, filter design and the smoking regimen., Conclusions: The addition of sufficient charcoal to cigarette filters is known to remove many volatile compounds and can potentially reduce deliveries of certain semi-volatile compounds under some machine smoking regimens. Less volatile compounds, with a significant portion in the particulate phase, are less available for selective filtration by charcoal-containing filters than the more volatile compounds that reside predominantly in the gas phase.

Of the chemicals identified to date in mainstream cigarette smoke with known toxicological properties, the volatile organic compounds (VOCs) are considered the most hazardous group owing to their high abundance and toxicity. In this research we evaluate a recently introduced line of cigarettes that contain charcoal in their filters. The amount of charcoal in these filters ranged from 45 mg to 180 mg and were either dispersed among the filter material or contained in a small cavity in the filter segment. Charcoal has long been used for removing VOCs from both water and air. Our findings indicate that these cigarettes reduce machine generated mainstream smoke deliveries of a wide range of VOCs compared to a similar, non-charcoal filtered, cigarette. However, this reduction is dependent not only on the amount of charcoal present but also on the volume of smoke being drawn through the filter. While a brand with 45 mg charcoal reduces VOC delivery under ISO smoking conditions, charcoal saturation and breakthrough occur under more intense smoking conditions. Breakthrough is minimised for brands with the most charcoal. Overall, the brands with the most charcoal are effective at reducing VOC deliveries under even intense smoking conditions.