Abstract
The relationship between biomarkers of exposure to cigarette smoke in 24h urine samples collected from groups of 80 smokers (44 males, 36 females) and 40 never smokers (17 males, 23 females) at two centers in Europe was studied. Eight biomarkers (nicotine, cotinine, hydroxycotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and all of the respective glucuronide conjugates) were measured. Subjects from the two centers were pooled and biomarker data analyzed according to the machine smoked tar yield of the brand each subject smoked and the recorded number of cigarettes smoked per day (CPD). A statistically significant relationship between CPD and all of the biomarkers analyzed was found. Smokers of less than 11 CPD had the lowest mean 24h urinary concentrations for all biomarkers measured. However, if the amount of constituent obtained from each cigarette smoked was calculated, then the amount of nicotine obtained per cigarette was highest in this group although the variation was also greatest for this group. The amount of NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone, the parent molecule of NNAL) obtained per cigarette was not statistically significantly different across all groups. In conclusion, these results confirm the reliability of 24h urinary total nicotine and NNAL concentrations as biomarkers of exposure to specific cigarette smoke constituents across two centers in Europe. These measurements may provide an objective alternative to CPD when grouping smokers for are studies of other endpoints.
Highlights
Cigarette smoke is a complex mixture of over 5000 different chemicals that partition between a gaseous and a particulate phase [1]
A statistically significant positive trend with the number of cigarettes smoked per day (CPD) was observed for all the exposure biomarkers studied (Table 1)
In Fig. (1), the relationship between total nicotine metabolites or total NNAL and the number of CPD is shown. For both biomarkers there is a clear linear trend across the groups from never smokers to smokers of 25CPD. From these data the average contribution of each cigarette smoked were calculated by dividing the concentration of the biomarkers by the CPD, which is shown in Fig. (2)
Summary
Cigarette smoke is a complex mixture of over 5000 different chemicals that partition between a gaseous and a particulate phase [1]. These subjects were pooled and the original urinary biomarkers of exposure data from Leeds [9] and Messina [10] were re-examined with different statistical approaches This larger subject pool allowed us to examine sub-groups in cigarettes per day (CPD) categories that are different from the original recruiting criteria and to establish whether data obtained from two separate European areas is suitable for combination, allowing for possible lifestyle and cigarette brand differences. All subjects were divided into new sub-groups according to the number of CPD recorded in the clinical period and the ISO machine smoked tar yield of their cigarette brands as follows: Never smokers (n=40); 1-10 CPD,
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