The composition of cigarette smoke: a retrospective, with emphasis on polycyclic components

The difficulties encountered in extrapolating biological activity from ciga rette smoke composition provide generally applicable lessons as they are re presentative of the problems encountered with other complex mixtures, Resea rchers attempting to assess risk are faced with attempting to interpret dat a from a number of areas including: tobacco science: smoke/aerosol chemistr y specific to tobacco: sophisticated analytical chemistry applications and techniques for trapping, collecting, separating, and quantifying very speci fic compounds at nanogram to picogram levels; numerous biological testing m ethodologies; and animal models of tumors and carcinogenesis, Numerous hypo theses have been developed over the past five decades and tested with the t echnology of the day in attempts to interpret the biological activity of ci garette smoke in relation to the chemistry of this complex mixture, These h ypotheses fall into several categories discussed in this review: mechanisms of pyrogenesis of polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke ; levels of PAHs in cigarette mainstream smoke (MS) and its tumorigenicity in mouse skin-painting experiments; control of PAH levels in MS; chemical i ndicators of cigarette smoke condensate (CSC) tumorigenicity: control of le vels of MS components partitioned between the vapor phase and particulate p hase of MS; tumorigenic threshold limits of CSC and many of its components; tumorigenic aza-arenes in tobacco smoke; MS components reported to be cili astatic to smokers' respiratory tract cilia: anticarcinogenic tobacco-smoke components, Of 52 hypotheses reviewed in this paper, 15 have excellent data supporting the hypothesis based on today's technology, The remaining 37 hypotheses, al though originally plausible, have since become insupportable in light of ne w and contradictory data generated over the years, Such data were generated sometimes by the original authors of the hypotheses and sometimes by other investigators, The hypotheses presented today are less likely to be suppla nted because they are well conceived and have a strong mechanistic basis, T he challenge for the future is the generation and interpretation of data re lating the chemistry and biological activity associated with the dynamic an d complex mixture of tobacco smoke.