Reduction of aldehydes and hydrogen cyanide yields in mainstream cigarette smoke using an amine functionalised ion exchange resin

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is a well recognized cause of diseases such as lung cancer, chronic obstructive pulmonary disease and cardiovascular disease. Of the more than 5000 identified species in cigarette smoke, at least 150 have toxicological activity. For example, formaldehyde and acetaldehyde have been assigned as Group 1 and Group 2B carcinogens by IARC, and hydrogen cyanide has been identified as a respiratory and cardiovascular toxicant. Active carbon has been shown to be an effective material for the physical adsorption of many of the smoke volatile species. However, physical adsorption of acetaldehyde, formaldehyde and also hydrogen cyanide from smoke is less effective using carbon. Alternative methods for the removal of these species from cigarette smoke are therefore of interest. A macroporous, polystyrene based ion-exchange resin (Diaion^®CR20) with surface amine group functionality has been investigated for its ability to react with aldehydes and HCN in an aerosol stream, and thus selectively reduce the yields of these compounds (in particular formaldehyde) in mainstream cigarette smoke.</p> <p>Results</p> <p>Resin surface chemistry was characterized using vapour sorption, XPS, TOF-SIMS and ¹⁵N NMR. Diaion^®CR20 was found to have structural characteristics indicating weak physisorption properties, but sufficient surface functionalities to selectively remove aldehydes and HCN from cigarette smoke. Using 60 mg of Diaion^®CR20 in a cigarette cavity filter gave reductions in smoke formaldehyde greater than 50% (estimated to be equivalent to >80% of the formaldehyde present in the smoke vapour phase) independent of a range of flow rates. Substantial removal of HCN (>80%) and acetaldehyde (>60%) was also observed. The performance of Diaion^®CR20 was found to be consistent over a test period of 6 months. The overall adsorption for the majority of smoke compounds measured appeared to follow a pseudo-first order approximation to second order kinetics.</p> <p>Conclusions</p> <p>This study has shown that Diaion^®CR20 is a highly selective and efficient adsorbent for formaldehyde, acetaldehyde and HCN in cigarette smoke. The reductions for these compounds were greater than those achieved using an active carbon. The results also demonstrate that chemisorption can be an effective mechanism for the removal of certain vapour phase toxicants from cigarette smoke.</p

Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

<p>Abstract</p> <p>Background</p> <p>Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia.</p> <p>Methods</p> <p>Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments.</p> <p>Results</p> <p>Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells.</p> <p>Conclusions</p> <p>We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.</p

Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

<p>Abstract</p> <p>Background</p> <p>Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke), a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS) impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER) functioning, our data highlighted a defensive role for the unfolded protein response (UPR) program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer.</p> <p>Methods</p> <p>Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry.</p> <p>Results</p> <p>We show that: 1) CS induces ER stress and activates components of the UPR; 2) reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3) CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4) several major UPR regulators are increased either in expression (i.e., BiP and eIF2α) or phosphorylation (i.e., phospho-eIF2α) in a majority of human lung cancers.</p> <p>Conclusion</p> <p>These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have diagnostic and/or therapeutic potential. Furthermore, we speculate that upregulation of UPR regulators (in particular BiP) may provide a pro-survival advantage by increasing resistance to cytotoxic stresses such as hypoxia and chemotherapeutic drugs, and that UPR induction is a potential mechanism that could be attenuated or reversed resulting in a more efficacious treatment strategy for lung cancer.</p

Scientific assessment of the use of sugars as cigarette tobacco ingredients: A review of published and other publicly available studies

Sugars, such as sucrose or invert sugar, have been used as tobacco ingredients in American-blend cigarettes to replenish the sugars lost during curing of the Burley component of the blended tobacco in order to maintain a balanced flavor. Chemical-analytical studies of the mainstream smoke of research cigarettes with various sugar application levels revealed that most of the smoke constituents determined did not show any sugar-related changes in yields (per mg nicotine), while ten constituents were found to either increase (formaldehyde, acrolein, 2-butanone, isoprene, benzene, toluene, benzo[k]fluoranthene) or decrease (4-aminobiphenyl, N-nitrosodimethylamine, N-nitrosonornicotine) in a statistically significant manner with increasing sugar application levels. Such constituent yields were modeled into constituent uptake distributions using simulations of nicotine uptake distributions generated on the basis of published nicotine biomonitoring data, which were multiplied by the constituent/nicotine ratios determined in the current analysis. These simulations revealed extensive overlaps for the constituent uptake distributions with and without sugar application. Moreover, the differences in smoke composition did not lead to relevant changes in the activity in in vitro or in vivo assays. The potential impact of using sugars as tobacco ingredients was further assessed in an indirect manner by comparing published data from markets with predominantly American-blend or Virginia-type (no added sugars) cigarettes. No relevant difference was found between these markets for smoking prevalence, intensity, some markers of dependence, nicotine uptake, or mortality from smoking-related lung cancer and chronic obstructive pulmonary disease. In conclusion, thorough examination of the data available suggests that the use of sugars as ingredients in cigarette tobacco does not increase the inherent risk and harm of cigarette smoking

Problems with the Tobacco Products Scientific Advisory Committee (TPSAC) List of Harmful or Potentially Harmful Tobacco and/or Tobacco Smoke Components

Abstract The draft initial list of harmful or potentially harmful tobacco and/or smoke components prepared by the Constituent Subcommittee of the Tobacco Products Scientific Advisory Committee (TPSAC) differs significantly from the similar lists prepared by Hoffmann and colleagues who had over four decades of experience and knowledge in tobacco and/or tobacco smoke components and their chemical and biological properties. The draft list comprises 106 components, 60 of which were included in the recent Hoffmann et al. lists but does not include nine of the Hoffmann-listed components. All of the 106 components appear in a list by Rodgman and Green of 162 tobacco and/or tobacco smoke components, each of which was defined as biologically adverse at one time or another over the previous years by one or more investigators. As with the Hoffmann et al. lists, the list by the TPSAC Constituent Subcommittee contains numerous anomalies. · Three harmful components (dibenz[a, j]acridine, dibenz[a, h]acridine, 7H-dibenzo[c, g]carbazole) first reported in tobacco smoke in the 1960s that were not confirmed over the next forty years by many talented investigators in Japan, Germany, and the USA, including several at the U.S. Department of Agriculture (USDA). · Two harmful components (arsenic, N-nitrosodiethanolamine) the levels of which have decreased significantly because their precursors have not been used in tobacco agronomy for over three decades. · The many water-soluble components that reach the lung at a much reduced level to exert their ciliastasis. · A component (chrysene) that the International Agency for Research on Cancer (IARC) has removed from its tumorigenicity listing, a decision accepted by Hoffmann et al. who removed chrysene from their more recent tobacco/tobacco smoke listings of adverse components. TPSAC gives no indication of the following: · The relationship between the per cigarette delivery of some of the harmful components and their level of permissibility by Occupational Safety &amp; Health Administration (OSHA). · The components on its list that significantly offset the adverse biological activity of several others of its listed components. · Many components in tobacco and/or tobacco smoke not listed by TPSAC have been reported to significantly reduce the adverse biological effect of several components on the TPSAC list plus several others.</jats:p