The Nature of Tumor-promoting Agents in Tobacco Products1

The results available so far suggest to us the following tentative conclusions. First, there are at least two agents extracted by aqueous barium hydroxide from commercial cigarette tobacco that are required simultaneously in order to exhibit tumor-promoting activity. One of the agents is soluble in 80% methanol and is probably soluble in 95% methanol. The other is insoluble in 80% methanol and may consist of a single compound of molecular weight approximately 1600 or else consists of a spectrum of compounds, some of large molecular weight and some of molecular weight 1600 or smaller. The fraction of large molecular weight is the more active on a per gram basis. Second, the activity of aqueous extracts is higher with commercial cigarette preparations than with fresh tobacco leaf that has not been sprayed with chemical agents. We cannot determine whether this increase is due to an increase in one or the other of the two components or whether both are increased concurrently during cigarette manufacture. Furthermore, we do not yet know whether the increase occurs during the curing and aging of the leaf, whether it occurs during cigarette formulation, or whether it is due to particular cultural practices in growing the leaf. In addition to those extracted with aqueous agents, other tumor promoters are extracted from tobacco with nonpolar solvents. It thus appears that the tumor-promoting activity of unburned tobacco products is due to various chemical com pounds of highly different characteristics. Whether any of these play a role in the development of oral carcinoma is yet to be determined. The tumor-promoting activity of cigarette smoke condensate cannot yet be related to the activity of the aqueous extracts of unburned tobacco. The promoting agents thus far demon strated in cigarette smoke condensate are either phenolic or nonpolar in nature. No clear relationship between the aqueous extracts of unburned tobacco and cigarette smoke promoters is apparent.