Phenanthrene (Phe) is a polycyclic aromatic hydrocarbon (PAH) with a bay region but unlike many of its higher homologues it is non-carcinogenic, and its metabolites are mainly excreted in urine. We have used urinary Phe metabolites as biomarkers of uptake plus metabolic activation of PAH. This is possible because Phe forms bay region diol epoxides structurally similar to those of the highly carcinogenic benzo[a]pyrene (BaP) but unlike BaP diol epoxides, Phe diol epoxides are non-carcinogenic. Phe diol epoxides are hydrolyzed in vivo and excreted in urine as Phe tetraols (PheT), biomarkers of exposure plus metabolic activation of PAH, with concentrations in human urine far greater than those of BaP tetraols. We developed a strategy in which deuterated Phe ([D10]Phe) was administered to humans and excretion of [D10]PheT and Phe phenols ([D9]PhOH) were monitored. In a clinical study of 170 cigarette smokers and 57 non-smokers, we demonstrated that the [D10]Phe bioactivation ratio was 2.3-4.8-fold higher (P&lt;0.01) in smokers than non-smokers showing for the first time in humans that induction of aryl hydrocarbon hydroxylase activity by smoking results in increased metabolic activation of PAH. Acrolein is a highly toxic and mildly carcinogenic constituent of cigarette smoke. We have used its urinary metabolites and tissue DNA adducts as biomarkers of acrolein exposure and possibly cancer risk. In one recent study, we developed a high resolution mass spectrometric method for determination of acrolein DNA adducts and etheno-DNA adducts in oral cells of cigarette smokers and non-smokers. Levels of these adducts in cells obtained by oral rinse were more than 20 times higher in smokers than non-smokers demonstrating a large effect of smoking on DNA damage in the oral cavity. Collectively these studies provide some important new insights on mechanisms of carcinogenesis in cigarette smokers.

Recent studies on phenanthrene and acrolein biomarkers in cigarette smokers and non-smokers

ACS Fall 2021

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