Smoking and Tobacco Control Monograph No. 7 
Furthermore, flue-cured tobacco leaves harvested from the lowest stalk 
position contain 0.08 to 0.65 percent nicotine, whereas those from the 
highest positions contain between 0.13 and 4.18 percent nicotine (Tso, 
1977). The resulting smoke differs widely in its concentration of toxic and 
tumorigenic agents (Hoffmann and Hoffmann, 1994a). Another example 
is the BaP content of the smoke generated from leaves harvested from the 
lowest stalk position, which ranges between 14.9 and 18.2 ng per cigarette, 
contrasted with BaP in the smoke from the leaves of the highest stalk 
position, which ranges between 23.2 and 35.2 ng per cigarette (Rathkamp 
et al., 1973). 
The first comparative study of the smoke of cigarettes made exclusively 
from bright, oriental, hurley, and Maryland tobacco was published by 
Wynder and Hoffmann (1963). The BaP levels in the smoke per cigarette 
(without filter tip) were 53, 44, 24, and 18 ng, respectively. The tars from the 
smoke of cigarettes made with bright and oriental tobaccos were significantly 
more tumorigenic than the tars from hurley and Maryland tobaccos (Wynder 
and Hoffmann, 1963). A large-scale study by NCI confirmed the observation 
that the smoke of hurley tobacco is lower in BaP and other carcinogenic 
agents than the smoke of bright tobacco and that the tar has less tumorigenic 
activity than the tar from bright tobacco (National Cancer Institute, 1980). 
During the past three decades, the nitrate content of the U.S. cigarette 
blend increased from 0.3 to 0.5 percent to 0.6 to 1.35 percent (U.S. 
Department of Health and Human Services, 1981; Fischer et al., 1990). 
During smoking, the nitrates in tobacco give rise to nitrogen oxides that 
scavenge C,H-radicals and thereby inhibit the pyrosyn thesis of carcinogenic 
PAHs; at the same time, nitrogen oxides are involved in the formation of 
nitrosamines from secondary and tertiary amines in tobacco (Rathkamp and 
Hoffmann, 1970; Hoffmann et al., 1994). The result is that today the smoke 
of the U.S. blended cigarette has lower concentrations of PAHs but higher 
concentrations of N-nitrosamines than the smoke of the U.S. blended 
cigarette three decades ago. Figure 7 shows the decrease per cigarette of 
BaP from 50 ng in 1965 to 20 ng in 1992 and the concomitant increase of 
the levels of the organ-specific lung carcinogen 4-(methylnitrosamino)-l- 
(3-pyridyl)-l-butanone (NNK) from 110 ng in the late 1970's to 176 ng in 
1992. These data pertain to the smoke of a leading United States nonfilter 
cigarette. NNK is formed from nicotine during tobacco processing and 
smoking (Hoffmann and Hoffmann, 1994a). In laboratory animals, 
carcinogenic PAHs induce primarily squamous cell carcinoma, whereas 
NNK elicits mainly adenocarcinoma in the peripheral lung. One major 
reason for the steep ascent of lung adenocarcinoma incidence in cigarette 
smokers in the United States compared with the more modest rise of 
squamous cell carcinoma may lie in the more intense smoking of the low- 
nicotine cigarette. The deeper inhalation of the smoke from these cigarettes 
has led to higher yields of NNK and lower yields of BaP in the smoke of the 
more recent cigarettes. Fhis modification has created a different profile of 
smoke carcinogens that is likely reflected in the changed tumor morphology 
that has emerged since the 1960's (Wynder and Hoffmann, 1994). 
30 
