NOV/DEC 2005
Volume 11 - No. 4
SRNT Newsletter
Nov/Dec 2005, Volume 11, Number 4
Research Activities at a Featured Program:
Tobacco Harm Reduction Research at
The University of Minnesota Transdisciplinary Tobacco
Research Center (UMN TTURC)
Dorothy Hatsukami and Stephen Hecht, co-directors of the UNM TTURC |
Exploring the effects of cigarette reduction
Studies examining the effects of cigarette reduction have focused on two main goals: 1) to determine the dose-response relationship between cancer and cardiovascular biomarkers with the amount of tobacco exposure; 2) and to determine if cigarette reduction is a viable treatment option. The main conclusions from these studies were the following:
- Researchers observed a dose-response relationship between biomarkers for carcinogen exposure and amount of cigarettes smoked. However, cigarettes per day is not necessarily a reliable measure of toxin exposure; it may underestimate tobacco toxin exposure at low levels of smoking or overestimate exposure at high levels of smoking (Joseph et al., in press).
- Smokers who reduce cigarettes also significantly reduce their exposure to carcinogens (Hecht, Murphy, Carmella, et al., 2004) and reduce cardiovascular risk factors (Hatsukami, Kotlyar, Allen, et al., in press), but these reductions are modest at best. For example, when smokers reduced their daily cigarette use by 55% to 90%, their total NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) levels only went down by 27% to 51%. Even a 90% reduction in cigarette use produced a total NNAL reduction of only 46%. Thus, reducing cigarette use by 90% may not be enough to reduce carcinogen levels sufficiently.
- Animal studies show that high doses of nicotine infusion — that is, levels that simulate arterial levels of nicotine observed during nicotine self-administration — result in significant reductions in nicotine self-administration (LeSage, Keyler, Collins, et al, 2004). However, human trials involving the use of three nicotine patches result in a modest reduction in cigarette intake (a mean of about 50%), with a great deal of individual variability.
- Smokers with cardiovascular disease who are not interested in stopping smoking and who were assigned to a smoking-reduction treatment did not significantly benefit (compared with usual care) when assessed by clinical or biomarker outcomes. However, the smoking reduction intervention did not deter them from quitting (Joseph, Hecht, Murphy, et al., 2005).
Demystifying modified tobacco products
UMN TTURC is one of several organizations leading the endeavor to scientifically evaluate the toxicity levels of what
are called potentially reduced-exposure tobacco products, or PREPs. Over the past decade, many tobacco companies
have introduced PREPs into the marketplace. Examples include Omni, Eclipse, Accord, Ariva, and Swedish moist snuff or
snus. From a consumer's perspective, the implication may be that these products can reduce disease risk by reducing
exposure to toxins. Evaluating actual levels of toxin exposure is therefore essential to determining whether PREPs are indeed as
risk-reducing as their advertisements claim. As part of this effort, UMN TTURC researchers have been
examining modified tobacco products (e.g., products with reduced toxins such as Omni, snus and Ariva)
compared to medicinal nicotine. The results thus far suggest that most of the modified tobacco products
have greater amounts of carcinogen exposure than medicinal nicotine, and the claims of reduction that are
made for the tobacco products based on machine-determined
methods do not concur with the extent observed in these human studies
(Hatsukamik
, Lemmonds, Zhang, et al, 2004) The results from these studies
indicate a need for strong regulatory oversight of these products. (Hatsukami & Hecht, 2005; Hecht &
Hatsukami, 2005).
Singling out secondhand smoke
Lung cancer has become an ever-increasing threat in those exposed to environmental tobacco smoke (ETS); it is the cause of more than 3,000 lung cancer deaths in nonsmokers each year in the United States. But despite the reality of these statistics, public opinion cannot yet uniformly support the adoption of smoking ordinances that prohibit smoking in public venues. To inform the debate, UMN TTURC researchers have conducted studies evaluating carcinogen exposure in those nonsmokers patronizing a casino (Anderson, Kliris, Murphy, et al, 2003) or working in bars and restaurants that allowed smoking (Tulunay, Hecht, Carmella, et al., 2005). Both studies demonstrated significant increases in nonsmokers' NNAL levels when they were exposed to smoky environments. NNAL levels in nonsmoking casino patrons increased more than two-fold. In addition, nonsmoking hospitality employees had up to 4.5 times more total NNAL in their bodies after their shift. Since NNAL is a metabolite of the tobacco-specific lung carcinogen NNK, these results clearly indicate that cancer-causing chemicals increase in nonsmokers when they are exposed to secondhand smoke.
The work at hand - And ahead
Recently, the National Institutes of Health renewed UMN TTURC's grant for another five years. This renewal will allow UMN TTURC to continue its fundamental mission while also addressing new research projects. Conceptually, UMN TTURC is now examining tobacco exposure reduction from a rather different approach—primarily, by considering tobacco addiction as a chronic disorder that demands therapies not only to halt symptoms (e.g., cessation treatments) but also to reduce or lessen symptoms (e.g., treatments to lower toxin exposure) for smokers who are unsuccessful in quitting. With this context in mind, the organization is currently pursuing research projects that will help 1) determine what biomarkers can predict lung cancer occurrence in smokers, 2) better understand what individual differences exist in tobacco-harm reduction, 3) identify the effects of various exposure reduction strategies in humans, and 4) assess the efficacy of "longitudinal" or "chronic care models" (as opposed to discrete therapies) for treating smokers who want to quit.
Jeanne Mettner is a science writer/communications consultant for UMN TTURC.
References
Anderson, K.A., Kliris, J., Murphy, L., et al. (2003). Metabolites of a tobacco-specific lung carcinogen in nonsmoking casino patrons. Cancer Epidemiology, Biomarkers & Prevention, 12, 1544-1546.
Hatsukami, D.K., & Hecht, S.S. (2005). Hope or Hazard? What research tells us about "potentially reduced-exposure" tobacco products. Published May 5, 2005. Available at http:/ /www.tturc.umn.edu.
Hatsukami, D,K,, Kotlyar, M, Allen S, et al. (in press). Effects of cigarette reduction on cardiovascular risk factors and subjective measures. Chest.
Hatsukami, D.K., Lemmonds, C., Zhang, Y., et al. (2004). Evaluation of carcinogen exposure in people who used "reduced exposure" tobacco products. Journal of the National Cancer Institute, 96, 844-852.
Hecht, S. & Hatsukami, D. (2005). Reducing harm caused by tobacco: research findings from the University of Minnesota. Minnesota Medicine,88, 40-43.
Hecht, S.S., Murphy, S.E., Carmella, S.G., et al. (2004). Effects of reduced cigarette smoking on the uptake of a tobacco- specific lung carcinogen. Journal of the National Cancer Institute, 96, 107-115.
Joseph, A.M., Hecht, S.S., Murphy, S.E., Carmella, S.G., Le, C.T., Zhang, Y., Han, S., & Hatsukami, D,K. (in press). Relationships between cigarette consumption and biomarkers of tobacco toxin exposure. Cancer Epidemiology, Biomarkers and Prevention.
Joseph, A.M., Hecht, S.S., Murphy, S.E., et al. (2005). A randomized controlled trial of smoking reduction in heart disease patients. Abstract presented at the Society for Research on Nicotine and Tobacco 11th Annual Meeting, March.
LeSage, M.G., Keyler, D.E., Collins, G., et al. (2003). Effects of continuous nicotine infusion on nicotine self-administration in rats: Relationship between continuously infused and self- administered nicotine doses and serum concentrations. Psychopharmacology, 170, 278-286.
Tulunay, O.E., Hecht, S.S., Carmella, S.G., et al. (2005). Urinary metabolites of a tobacco-specific lung carcinogen in nonsmoking hospitality workers. Cancer Epidemiology, Biomarkers & Prevention, 14, 1283-1286.