Contributions to Tobacco and Nicotine Research (Oct 2006)
The Composition of Cigarette Smoke: A Chronology of the Studies of Four Polycyclic Aromatic Hydrocarbons
Abstract
Among the polycyclic aromatic hydrocarbons (PAHs), a major class of identified cigarette mainstream smoke (MSS) components, are several shown to be tumorigenic in laboratory animals and suspect as possible tumorigens to humans. To date, nearly 540 PAHs have been completely or partially identified in tobacco smoke [Rodgman and Perfetti (1)]. A detailed chronology is presented of studies on four much discussed PAHs identified in tobacco smoke, namely, benz[a]anthracene (B[a]A), its 7,12-dimethyl derivative (DMB[a]A), dibenz[a, h]anthracene (DB[a, h]A), and benzo[a]pyrene (B[a]P). Of the four, DMB[a]A, DB[a, h]A, and B[a]P are considered to be potently tumorigenic on mouse skin painting and subcutaneous injection. Opinions on the tumorigenicity of B[a]A to mouse skin vary. DMB[a]A is frequently used in tumorigenicity studies as an initiator. Examination of the number of tobacco smoke-related citations listed for these four PAHs reveals the enormous effort devoted since the early 1950s to B[a]P vs. the other three. An annotated chronology from 1886 to date describes the tobacco smoke-related research pertinent to these four PAHs, their discovery, isolation and/or identification, quantitation, and contribution to the observed biological activity of MSS or cigarette smoke condensate (CSC). Much of the major literature on these four PAHs in tobacco smoke is presented in order to permit the reader to decide whether the current evidence is sufficient to classify them as a health risk to smokers. There has certainly been a tremendous effort by researchers to learn about these PAHs over the past several decades. Each of these PAHs when tested individually has been shown to possess the following biological properties: 1) Mutagenicity in certain bacterial situations, 2) tumorigenicity in certain animal species, to varying degrees under various administration modes, and 3) a threshold limit below which no tumorigenesis occurs. For more than five decades, it has been known that some of the PAHs, when co-administered in pairs of a potent tumorigen plus a non-tumorigen or weak tumorigen, show inhibitory effects on the tumorigenicity of the most potent, e.g., B[a]A plus DB[a, h]A; B[a]A plus B[a]P; anthracene plus DB[a, h]A. Over the period studied, some regulatory agencies considered these tobacco smoke PAHs to be serious health concerns, others did not.