These results show that total NNAL is not only an exposure biomarker for the lung carcinogen NNK but also a risk biomarker for lung cancer (Church et al., 2008). Some of these biomarkers were used to assess the role of cigarette reduction as a potential method selleck chemical to reduce tobacco toxicant exposure and perhaps disease risk (Hatsukami et al., 2005; Hecht, Carmella, et al., 2004; Hecht, Murphy, et al., 2004). Smokers were recruited and asked to systematically decrease their cigarette intake by 75%; levels of total NNAL and 1-HOP and cardiovascular risk factors were measured. Statistically significant reductions in lung carcinogen uptake and cardiovascular risk factors were observed with cigarette reduction. However, the observed decreases were generally modest, due to compensatory smoking, and sometimes transient.
In animal studies, compensatory nicotine self-administration (NSA) was observed when duration of access to nicotine or nicotine dose was reduced (Harris, Burroughs, Pentel, & LeSage, 2008), and lower baseline self-administration was a strong predictor of greater compensation. In a clinical trial that compared cigarette reduction and cessation among smokers who had cardiovascular disease but were not interested in quitting, smoking reduction failed to improve clinical and biological markers of cardiac disease (Joseph et al., 2008). These results suggest that cigarette reduction does no harm but is not likely to provide any health benefits or may not necessarily lead to greater cessation than a simple message to quit.
Other studies examined whether modified cigarettes or smokeless tobacco (ST) or switching cigarette smokers to ST would lead to significant reductions in toxicant exposure compared with medicinal nicotine products. These studies showed (a) no difference in levels of total NNAL, 1-HOP, and cotinine in smokers of regular, light, and ultra-light cigarettes, respectively, which is consistent with epidemiological studies showing that these cigarettes do not lead to reduced risk for cancer (Hecht et al., 2005); (b) significant but only modest reductions in carcinogen exposure when smokers switched from conventional to modified reduced carcinogen cigarettes (Hatsukami et al., 2004); (c) a significant reduction in carcinogens when ST users switched from a conventional U.S. product to Swedish snus (Hatsukami et al.
) GSK-3 and when smokers switched to Swedish snus or tobacco lozenge (Mendoza-Baumgart et al., 2007); and (d) the greatest reductions occurring with medicinal nicotine products. These studies support the concept of a continuum of risk associated with different types of nicotine-containing products (Hatsukami et al., 2007). ST products may hold some promise for tobacco harm reduction, although medicinal nicotine products clearly lead to less toxicant exposure.