Nicotine addiction is the most common serious medical problem in the country. Tobacco use is responsible for 30% of cancer deaths in the United States and 90% of all lung cancer deaths. The physical addiction to nicotine explains why over 30% of Americans continue to smoke or use tobacco despite their desires and efforts to quit. The testimony summarized in this paper recommends four broad strategies for preventing tobacco-caused cancers in the United States: a) mandating and reimbursing effective treatments for nicotine addiction; b) increasing Federal and state tobacco excise taxes and earmarking a fraction of tax revenues for tobacco prevention and cessation; c) enacting other policy changes to prevent tobacco use and addiction among children, including expanded clean indoor air legislation, comprehensive youth tobacco access legislation, and the regulation of tobacco products and their advertising and promotion; and d) expanding tobacco control research and critical Federal research support. Specific recommendations are given for each broad strategy.
New molecular techniques focus a genetic lens on nicotine addiction. Given the medical and economic costs associated with smoking, innovative approaches to smoking cessation and prevention must be pursued.
But can sound research be manipulated by the tobacco industry?
The chronological narrative of this paper was created using iterative reviews of primary sources (the Legacy Tobacco Documents), supplemented with secondary literature to provide broader context. The empirical data inform an ethics and policy analysis of tobacco-industry funded research.
The search for a genetic basis for smoking is consistent with industry’s decades-long plan to deflect responsibility away from the tobacco companies and onto individuals’ genetic constitutions. Internal documents reveal longstanding support for genetic research as a strategy to relieve the tobacco industry of its legal responsibility for tobacco-related disease.
Industry may turn the findings of genetics to its own ends, changing strategy from creating a “safe” cigarette to defining a “safe” smoker.
tobacco industry; genetics; legacy tobacco documents
Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized byCYP2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.
nicotine; addiction; smoking; pharmacogenetics; varenicline; bupropion
Tobacco product testing is a critical component of the Family Smoking Prevention and Tobacco Control Act (FSPTCA), which grants the Food and Drug Administration the authority to regulate tobacco products. The availability of methods and measures that can provide accurate data on the relative health risks across types of tobacco products, brands, and subbrands of tobacco products on the validity of any health claims associated with a product, and on how consumers perceive information on products toxicity or risks is crucial for making decisions on the product's potential impact on public health. These tools are also necessary for making assessments of the impact of new indications for medicinal products (other than cessation) but more importantly of tobacco products that may in the future be marketed as cessation tools.
To identify research opportunities to develop empirically based and comprehensive methods and measures for testing tobacco and other nicotine-containing products so that the best science is available when decisions are made about products or policies.
Literature was reviewed to address sections of the FSPTCA relevant to tobacco product evaluation; research questions were generated and then reviewed by a committee of research experts.
A research agenda was developed for tobacco product evaluation in the general areas of toxicity and health risks, abuse liability, consumer perception, and population effects.
A cohesive, systematic, and comprehensive assessment of tobacco products is important and will require building consensus and addressing some crucial research questions.
Smoking is an important cause of morbidity and mortality. Preventing and halting tobacco use are worthy strategies to improve the overall health of any population. Smoking and tobacco use begin during early adolescence, and most smokers try their first cigarette by age 12. A variety of psychosocial factors are involved in the initiation of tobacco use by adolescents. Strategies to prevent tobacco use should address these factors. Cessation efforts are hampered by nicotine addiction, which occurs in adolescents in a manner comparable to adults. Physicians and health care providers can assist adolescents in their attempts to quit tobacco use. A combination of counseling, peer and family support and, for some, nicotine replacement therapy, is the best approach to tobacco cessation. This paper reviews the findings of the major epidemiologic surveys of adolescent tobacco use and suggests strategies that health care providers can employ to reduce tobacco use among their adolescent patients.
OBJECTIVE: To identify journals that have a focus on human nicotine/smoking research and to investigate the coverage of smoking in "high-impact" journals. DESIGN: The MEDLINE computer database was searched for English-language articles on human studies published in 1988-1992 using "nicotine", "smoking", "smoking cessation", "tobacco", or "tobacco use disorder" as focus descriptors. This search was supplemented with a similar search of the PSYCLIT computer database. Fifty-eight journals containing at least 20 nicotine/smoking articles over the five years were analysed for impact factor (IF; citations per article). RESULTS: Among the journals with the highest percentage of nicotine- or smoking-focused articles (that is, 9-39% of their articles were on nicotine/smoking), Addiction, American Journal of Public Health, Cancer Causes and Control, Health Psychology, and Preventive Medicine had the greatest IF (range = 1.3-2.6). Among the journals highest in impact factor (IF > 3), only American Journal of Epidemiology, American Review of Respiratory Disease, Journal of the National Cancer Institute, and Journal of the American Medical Association published more than 10 nicotine/smoking articles per year (3-5% of all articles). Of these, only Journal of the American Medical Association published a large number of nicotine/smoking articles (32 per year). CONCLUSIONS: Although smoking causes 20% of all mortality in developed countries, the topic is not adequately covered in high-impact journals. Most smoking research is published in low-impact journals.
Life-style and tobacco addiction is the major risk factors for cancer progression in all over the world. Knowledge gaps between tobacco addiction, obesity and cancer in Indian patients brought an interdisciplinary group of investigators together to discuss the present study.
Patients and Methods:
We calculated the body mass index (BMI) of all the patients (N = 927) who were diagnosed with cancer for its treatment. National Institutes of Health (NIH) criteria were used to categorize the patients. All the patients of this disease could be contacted in person to find out the history of the disease.
The frequency of addiction in urban cancer patient was found to be about 53.3% and in a rural area it was only 33.7%. Tobacco addiction was independently associated with younger age of cancer patient (odds ratio [OR] 2.242; 95% Confidence interval (CI) 1.653-3.042), obese (OR 7.433; 95% CI 3.746-14.750), overweight (OR 4.676; 95% CI 3.381-6.468) and advanced stage of cancer (OR 11.950; 95% CI 5.283-27.030).
Tobacco consumption appears to be a major contributor to cancer in younger age with elevated BMI in India. Rapid changes in diet and life-style, increase in tobacco consumption appear to be strongly associated with the carcinoma in this middle-income country.
Addiction; body mass index; cancer; cancer stage; obesity; tobacco
Introduction: The vast majority of tobacco smokers seeking to quit will relapse within the first month of abstinence. Currently available smoking cessation agents have limited utility in increasing rates of smoking cessation and in some cases there are notable safety concerns related to their use. Hence, there is a pressing need to develop safer and more efficacious smoking cessation medications. Methods: Here, we provide an overview of current efforts to develop new pharmacotherapeutic agents to facilitate smoking cessation, identified from ongoing clinical trials and published reports. Results: Nicotine is considered the major addictive agent in tobacco smoke, and the vast majority of currently available smoking cessation agents act by modulating nicotinic acetylcholine receptor (nAChR) signaling. Accordingly, there is much effort directed toward developing novel small molecule therapeutics and biological agents such as nicotine vaccines for smoking cessation that act by modulating nAChR activity. Our increasing knowledge of the neurobiology of nicotine addiction has revealed new targets for novel smoking cessation therapeutics. Indeed, we highlight many examples of novel small molecule drug development around non-nAChR targets. Finally, there is a growing appreciation that medications already approved for other disease indications could show promise as smoking cessation agents, and we consider examples of such repurposing efforts. Conclusion: Ongoing clinical assessment of potential smoking cessation agents offers the promise of new effective medications. Nevertheless, much of our current knowledge of molecular mechanisms of nicotine addiction derived from preclinical studies has not yet been leveraged for medications development.
Tobacco smoking remains the most established cause of lung carcinogenesis and other disease processes. Over the last 50 years, tobacco refinement and the introduction of filters have brought a change in histology, and now adenocarcinoma has become the most prevalent subtype. Over the last decade, smoking also has emerged as a strong prognostic and predictive patient characteristic along with other variables. This article briefly reviews scientific facts about tobacco, and the process and molecular pathways involved in lung carcinogenesis in smokers and never-smokers. The evidence from randomised trials about tobacco smoking’s impact on lung cancer outcomes is also reviewed.
Tobacco Smoking; Lung Neoplasms; Nicotine; EML4 ALK fusion protein, human; K-Ras Gene; Receptor, Epidermal Growth Factor; Carcinogens
Smoking cessation is necessary to reach a higher quality of life, and, for a cancer patient, it represents an important step in improving the outcome of both prognosis and therapy. Being a cancer patient addicted to nicotine may be a critical situation. We conducted a survey to monitor how many comprehensive cancer centres in Italy have an outpatient smoker clinic and which kinds of resources are available. We also inquired about inpatient services offering psychological and pharmacological support for smoking cessation, reduction, or care of acute nicotine withdrawal symptoms. What we have witnessed is a significant gap between guidelines and services. Oncologists and cancer nurses are overscheduled, with insufficient time to engage in discussion on a problem that they do not consider directly related to cancer treatment. Furthermore, smoking habits and limited training in tobacco dependence and treatment act as an important barrier and lead to the undervaluation of smokers' needs.
The prevalence of tobacco use, both cigarette smoking and smokeless, including iqmik (homemade smokeless tobacco prepared with dried tobacco leaves mixed with alkaline ash), and of tobacco-related cancer is high in Alaskan Native people (AN). To investigate possible mechanisms of increased cancer risk we studied levels of nicotine and tobacco-specific nitrosamines (TSNA) in tobacco products and biomarkers of tobacco toxicant exposure in Southwestern AN people.
Participants included 163 cigarette smokers, 76 commercial smokeless tobacco, 20 iqmik, 31 dual cigarette smokers and smokeless tobacco, and 110 nontobacco users. Tobacco use history, samples of tobacco products used, and blood and urine samples were collected.
Nicotine concentrations were highest in cigarette tobacco and TSNAs highest in commercial smokeless tobacco products. The AN participants smoked on average 7.8 cigarettes per day. Nicotine exposure, assessed by several biomarker measures, was highest in iqmik users, and similar in smokeless tobacco and cigarette smokers. TSNA exposure was highest in smokeless tobacco users, and polycyclic aromatic hydrocarbon exposure was highest in cigarette smokers.
Despite smoking fewer cigarettes per day, AN cigarette smokers had similar daily intake of nicotine compared to the general U.S. population. Nicotine exposure was greatest from iqmik, likely related to its high pH due to preparation with ash, suggesting high addiction potential compared to other smokeless tobacco products. TSNA exposure was much higher with smokeless tobacco than other product use, possibly contributing to the high rates of oral cancer.
Our data contribute to an understanding of the high addiction risk of iqmik use and of the cancer-causing potential of various forms of tobacco use among AN people.
Tobacco dependence is a complex phenomenon that is not fully understood. Nicotine is the main alkaloid in tobacco and the addictive compound of tobacco. It can improve both mood and cognitive functioning; these positive effects are strong reinforcements for smokers and contribute to their addiction. Opposite results also have been reported, however, and the effects of nicotine remain controversial. Recent epidemiological and empirical studies have indicated that smoking or nicotine or both may have protective effects against certain diseases. These findings have suggested that nicotine may be used as a therapeutic agent. However, because a variety of nicotinic cholinergic receptors are present in the brain, new agonist compounds may prove to be more effective than nicotine for therapeutic purposes. Studies are reviewed and the suggestion made that nicotine may prove useful as a tool to help us understand normal and pathological brain functioning.
Studies are under way to examine the neurogenetic factors contributing to smoking behaviors. The combined approaches of genomics, molecular biology, neuroscience, and pharmacology are expected to fuel developments in pharmacogenetics, to create new genetic tests, and ultimately to provide the basis for innovative strategies for smoking cessation and prevention. The emergence of a neurogenomic understanding of nicotine addiction is likely to induce fundamental changes in popular, clinical, and public health views of smoking, which could significantly shape existing practices and policies to reduce tobacco use. Still a nascent area of research, nicotine addiction provides an excellent case study through which to anticipate key ethical and policy issues in both behavioral genetics and the neurogenomics of addictive behaviors.
Cigarette smoking is highly correlated with the onset of a variety of human cancers, and continued smoking is known to abrogate the beneficial effects of cancer therapy. While tobacco smoke contains hundreds of molecules that are known carcinogens, nicotine, the main addictive component of tobacco smoke, is not carcinogenic. At the same time, nicotine has been shown to promote cell proliferation, angiogenesis, and epithelial-mesenchymal transition, leading to enhanced tumor growth and metastasis. These effects of nicotine are mediated through the nicotinic acetylcholine receptors that are expressed on a variety of neuronal and nonneuronal cells. Specific signal transduction cascades that emanate from different nAChR subunits or subunit combinations facilitate the proliferative and prosurvival functions of nicotine. Nicotinic acetylcholine receptors appear to stimulate many downstream signaling cascades induced by growth factors and mitogens. It has been suggested that antagonists of nAChR signaling might have antitumor effects and might open new avenues for combating tobacco-related cancer. This paper examines the historical data connecting nicotine tumor progression and the recent efforts to target the nicotinic acetylcholine receptors to combat cancer.
Smoking is a significant risk factor for pancreatic cancer, but the molecular mechanisms by which tobacco smoke components promote the growth and progression of these cancers are not fully understood. While nicotine, the addictive component of tobacco smoke, is not a carcinogen, it has been shown to promote the growth of non-small cell lung and pancreatic cancers in a receptor-dependent fashion. Here, we show that stimulation of pancreatic cancer cells with nicotine concentrations that are within the range of human exposure results in activation of Src kinase, which facilitated the induction of the inhibitor of differentiation-1 (Id1) transcription factor. Depletion of Id1 prevented nicotine-mediated induction of proliferation and invasion of pancreatic cancer cells, indicating that it is a major mediator of nicotine function. Nicotine could promote the growth and metastasis of pancreatic cancers orthotopically implanted into SCID mice; in addition, cells stably expressing a short hairpin RNA for Id1 did not grow or metastasize in response to nicotine. Nicotine could also confer resistance to apoptosis induced by gemcitabine in pancreatic cancer cells in vitro and depletion of Src or Id1 rendered the cells sensitive to gemcitabine. Further, nicotine could effectively inhibit the chemotherapeutic effects of gemcitabine on pancreatic tumors xenografted into mice. Clinical analyses of resected pancreatic cancer specimens demonstrated a statistically significant correlation between Id1 expression and phospho-Src, tumor grade/differentiation, and worsening overall patient survival. These results demonstrate that exposure to tobacco smoke components might promote pancreatic cancer progression, metastasis, and chemoresistance and highlight the role of Id1 in these processes.
Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiological levels of nicotine on lung tumor formation, tumor growth or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, NNK. Tumors that develop in this model have mutations in K-ras, which is a commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras-driven lung cancer, nicotine did not increase tumor number or size, and did not affect overall survival. Likewise, in a syngeneic model of lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable to those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiological data showing that NRT does not enhance lung cancer risk in former smokers.
Nicotine; NNK; K-ras; nicotine replacement therapy
Cigarette smoking is a mixture of thousands of compounds, many of which are carcinogens, such as NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]. Nicotine, as an addictive substance in cigarette, has been shown to promote growth of non-neuronal cells. It is unclear how nicotine cooperates with tobacco-related carcinogens during tumorigenesis. Here, by concurrent treatment of nicotine and NNK, we investigate the effect of the cooperation of these two compounds on cell growth and apoptosis in various different lung epithelial (RLE) or cancer (LKR) cells. We demonstrated that short-term nicotine exposure moderately activated mitogenic signaling pathways (such as PKC, ERK and Akt) and a mediocre protection against cisplatin-mediated apoptosis. In contrast, NNK strongly stimulated mitogenic signaling and rendered the cells a high resistance to cisplatin. The pre-ligation of nAChR by nicotine interfered with NNK-mediated mitogenic signaling and resistance to cisplatin, the magnitude of which was similar as that exposed to nicotine alone. Interestingly, a week after the exposure to nicotine or nicotine plus NNK, Bcl-2 expression was augmented, accompanied with the increased resistance to cisplatin-induced apoptosis. In comparison, long-term NNK treatment provided very little protection of the cells from cisplatin. We also showed that the combination treatment promoted more cells to grow in an anchorage-independent fashion than NNK exposure alone. Thus, the data suggest that through occupying nAChR, nicotine appears to modulate NNK-mediated signaling and persistently sustain pro-survival activities to promote transformation.
nicotine acetylcholine receptor; nitrosamines; mitogenic pathways; lung cells
Social smoking is increasingly prevalent and poses a challenge to traditional cessation practices. Tobacco companies conducted extensive research on social smokers long before health authorities did and marketed products to promote this smoking behavior.
Research is described and mechanisms identified that are used to promote social smoking to help improve cessation strategies in this growing group.
Searches from 2006 to 2008 of previously secret tobacco industry documents using keywords social smoker, light smoker, casual smoker, youth smoker, and occasional smoker, followed by snowball searching. Data analysis was conducted in 2008.
Tobacco industry research identified characteristics of social smokers that include: (1) denial of personal nicotine addiction; (2) self-categorization as a nonsmoker; (3) propensity for decreased tobacco use in response to smoke-free laws; (4) variations in age, education, ethnicity, and socioeconomic backgrounds; and (5) a perceived immunity to personal health effects of tobacco but fear of consequences to others. Tobacco companies developed marketing strategies aimed at social smokers, including “non–habit forming” cigarettes.
Previously considered a transient behavior, social smoking is also a stable consumption pattern. Focused clinical questions to detect social smoking are needed and may include, “Have you smoked any cigarettes or used any tobacco products in the past month?” as opposed to “Are you a smoker?” Clinicians should recognize that social smokers might be motivated to quit after education on the dangers of secondhand smoke rather than on personal health risks or with pharmacotherapy.
Tobacco addiction requires activation by nicotine of a variety of central nicotinic acetylcholine receptors (nAChRs). In animals, both nAChR antagonists and immunization against nicotine can reduce nAChR activation by nicotine and block a variety of addiction-relevant behaviors. However, clinical use of nAChR antagonists for smoking cessation is limited by dose-related side effects, and immunization does not reliably produce sufficient antibody levels in smokers to enhance smoking cessation rates. Combining these approaches may be one way of addressing the limitations of each while enhancing overall efficacy. This study examined the individual and combined effects of passive immunization with the monoclonal nicotine-specific antibody Nic311 and the nicotinic receptor antagonist mecamylamine (MEC) on nicotine’s discriminative stimulus effects. Rats were trained to discriminate 0.4 mg/kg nicotine from saline using a two-lever operant discrimination procedure. Antagonism of nicotine discrimination by Nic311 (160 mg/kg i.v.) and ascending doses of MEC (0.03, 0.1, 0.3, and 1.0 mg/kg s.c.) was assessed across four consecutive daily 2-min extinction test sessions using a 2 × 2 design. Nic311 alone produced a 24-48% reduction in % nicotine-lever responding (%NLR) across all four test sessions. MEC produced a dose-dependent decrease in %NLR, with no effect at the two lowest doses and 80-93% attenuation at the two highest doses. Nic311 combined with MEC significantly suppressed %NLR at every MEC dose (85-92% reduction across all four test sessions). Very low doses of MEC that were ineffective alone completely blocked nicotine discrimination when combined with Nic311. These data demonstrate that nicotine-specific antibodies and MEC can work synergistically to suppress the subjective effects of nicotine and suggest that low doses of MEC may significantly enhance the efficacy of immunotherapy.
nicotine; drug discrimination; mecamylamine; monoclonal nicotine-specific antibodies; rat
With the number of smokers worldwide currently on the rise, the regular failure of smokers to give up their tobacco addiction, the direct role of smoke (and, to a much lesser extent, nicotine) in most tobacco-related diseases, and the availability of less toxic (but still addictive) oral tobacco products, the use of oral tobacco in lieu of smoking for tobacco harm reduction (HR) merits assessment.
Instead of focusing on the activity itself, HR focuses on the risks related to the activity. Currently, tobacco HR is controversial, generally not discussed, and consequently, poorly evaluated.
In this paper, we try to pinpoint some of the main reasons for this lack of interest or reluctance to carry out or fund this type of research. In this paper we deal with the following issues: the status of nicotine in society, the reluctance of the mainstream anti-tobacco lobby toward the HR approach, the absence of smokers from the debate, the lack of information disseminated to the general population and politicians, the need to protect young people, the role of physicians, the future of HR research, and the role of tobacco companies.
Use of tobacco is singularly responsible for most cases of cancer and coronary artery disease (CAD). Efforts to stop tobacco-use need to be guided by social circumstances. It is believed that family milieu may play a role in tobacco addiction. We studied the prevalence and pattern of tobacco-use in families of 50 consecutive tobacco-user patients who presented to a tobacco-cessation clinic and compared with age- and gender-matched controls (non-users of tobacco). The tobacco-use rates were significantly higher in the family of patients with tobacco-use compared to the control group. We conclude that problems of tobacco-use are not related to individual phenomenon, and efforts for control of tobacco addiction must be focused on entire family.
Addiction; Family; Non-communicable disease; Public health; Tobacco; India
The emergency department (ED) visit provides a great opportunity to initiate interventions for smoking cessation. However, little is known about ED patient preferences for receiving smoking cessation interventions or correlates of interest in tobacco counseling.
ED patients at 10 US medical centers were surveyed about preferences for hypothetical smoking cessation interventions and specific counseling styles. Multivariable linear regression determined correlates of receptivity to bedside counseling.
Three hundred seventy-five patients were enrolled; 46% smoked at least one pack of cigarettes per day, and 11% had a smoking-related diagnosis. Most participants (75%) reported interest in at least one intervention. Medications were the most popular (e.g., nicotine replacement therapy, 54%), followed by linkages to hotlines or other outpatient counseling (33-42%), then counseling during the ED visit (33%). Counseling styles rated most favorably involved individualized feedback (54%), avoidance skill-building (53%), and emphasis on autonomy (53%). In univariable analysis, age (r = 0.09), gender (average Likert score = 2.75 for men, 2.42 for women), education (average Likert score = 2.92 for non-high school graduates, 2.44 for high school graduates), and presence of smoking-related symptoms (r = 0.10) were significant at the p < 0.10 level and thus were retained for the final model. In multivariable linear regression, male gender, lower education, and smoking-related symptoms were independent correlates of increased receptivity to ED-based smoking counseling.
In this multicenter study, smokers reported receptivity to ED-initiated interventions. However, there was variability in individual preferences for intervention type and counseling styles. To be effective in reducing smoking among its patients, the ED should offer a range of tobacco intervention options.
Smoking; Tobacco; Cigarettes; Emergency medicine; Counseling; Patient preference
In vitro toxicology studies of tobacco and tobacco smoke have been used to understand why tobacco use causes cancer and to assess the toxicological impact of tobacco product design changes. The need for toxicology studies has been heightened given that the FDA’s newly granted authority over tobacco products requires mandating performance standards for tobacco products and evaluate manufacturers’ health claims. The goal of this review is to critically evaluate in vitro toxicology methods related to cancer for assessing tobacco products and to identify related research gaps.
PubMed database searches were used to identify tobacco-related in vitro toxicology studies published since 1980. Articles published prior to 1980 with high relevance also were identified. The data was compiled to examine: 1) goals of the study; 2) methods for collecting test substances; 3) experimental designs; 4) toxicological endpoints, and; 5) relevance to cancer risk.
A variety of in vitro assays are available to assess tobacco and tobacco smoke that address different modes of action, mostly using non-human cell models. Smokeless tobacco products perform poorly in these assays. While reliable as a screening tool for qualitative assessments, the available in vitro assays have been poorly validated for quantitative comparisons of different products. Assay batteries have not been developed, although they exist for non-tobacco assessments. Extrapolating data from in vitro studies to human risks remains hypothetical.
In vitro toxicology methods are useful for screening toxicity, but better methods are needed for today’s context of regulation and evaluation of health claims.
Ames testing; cytotoxicity; genotoxicity; epigenetics; smoking machine
This paper identifies research priorities in evaluating the ways in which “genomic medicine”—the use of genetic information to prevent and treat disease—may reduce tobacco‐related harm by: (1) assisting more smokers to quit; (2) preventing non‐smokers from beginning to smoke tobacco; and (3) reducing the harm caused by tobacco smoking. The method proposed to achieve the first aim is “pharmacogenetics”, the use of genetic information to optimise the selection of smoking‐cessation programmes by screening smokers for polymorphisms that predict responses to different methods of smoking cessation. This method competes with the development of more effective forms of smoking cessation that involve vaccinating smokers against the effects of nicotine and using new pharmaceuticals (such as cannabinoid antagonists and nicotine agonists). The second and third aims are more speculative. They include: screening the population for genetic susceptibility to nicotine dependence and intervening (eg, by vaccinating children and adolescents against the effects of nicotine) to prevent smoking uptake, and screening the population for genetic susceptibility to tobacco‐related diseases. A framework is described for future research on these policy options. This includes: epidemiological modelling and economic evaluation to specify the conditions under which these strategies are cost‐effective; and social psychological research into the effect of providing genetic information on smokers' preparedness to quit, and the general views of the public on tobacco smoking.
OBJECTIVE—To assess the feasibility of reducing tobacco-caused disease by gradually removing nicotine from cigarettes until they would not be effective causes of nicotine addiction.
DATA SOURCES—Issues posed by such an approach, and potential solutions, were identified from analysis of literature published by the US Food and Drug Administration (FDA) in its 1996 Tobacco Rule, comments of the tobacco industry and other institutions and individuals on the rule, review of the reference lists of relevant journal articles, other government publications, and presentations made at scientific conferences.
DATA SYNTHESIS—The role of nicotine in causing and sustaining tobacco use was evaluated to project the impact of a nicotine reduction strategy on initiation and maintenance of, and relapse to, tobacco use. A range of potential concerns and barriers was addressed, including the technical feasibility of reducing cigarette nicotine content to non-addictive levels, the possibility that compensatory smoking would reduce potential health benefits, and whether such an approach would foster illicit ("black market") tobacco sales. Education, treatment, and research needs to enable a nicotine reduction strategy were also addressed. The Council on Scientific Affairs came to the following conclusions: (a) gradually eliminating nicotine from cigarettes is technically feasible; (b) a nicotine reduction strategy holds great promise in preventing adolescent tobacco addiction and assisting the millions of current cigarette smokers in their efforts to quit using tobacco products; (c) potential problems such as compensatory over-smoking of denicotinised cigarettes and black market sales could be minimised by providing alternate forms of nicotine delivery with less or little risk to health, as part of expanded access to treatment; and (d) such a strategy would need to be accompanied by relevant research and increased efforts to educate consumers and health professionals about tobacco and health.
CONCLUSIONS—The council recommends the following: (a) that cessation of tobacco use should be the goal for all tobacco users; (b) that the American Medical Association continue to support FDA authority over tobacco products, and FDA classification of nicotine as a drug and tobacco products as drug-delivery devices; (c) that research be encouraged on cigarette modifications that may result in less addicting cigarettes; (d) that the FDA require that the addictiveness of cigarettes be reduced within 5-10 years; (e) expanded surveillance to monitor trends in the use of tobacco products and other nicotine-containing products; (f) expanded access to smoking cessation treatment, and strengthening of the treatment infrastructure; and (g) more accurate labelling of tobacco products, including a more meaningful and understandable indication of nicotine content.
Keywords: American Medical Association; addiction; nicotine; smoking cessation