A Chemical Approach to Searching for Bioactive Ingredients in Cigarette Smoke

Cigarette smoke, a collection of many toxic chemicals, contributes to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease and cancer. Much work has been done on the chemical analysis of ingredients in cigarette smoke, but there are few reports on the active ingredients that can modify biomolecules. We used a sensitive liquid chromatography-mass spectrometry (LC/MS) and LC/MS/MS method to show that L-tyrosine (Tyr), an amino acid with a highly reactive hydroxyl group, readily reacts with cigarette smoke extract (CSE) at body temperature (37°C) to form various Tyr derivatives. Among these derivatives were N-(3-oxobutyl)-Tyr and two acetylated compounds, N-acetyl-Tyr and O-acetyl-Tyr, which were synthesized by reaction of Tyr with methyl vinyl ketone and acetic anhydride, respectively, at 37°C. The presence of methyl vinyl ketone and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). These results indicate that Tyr can easily react with active ingredients in CSE. The present analytical methods should aid the search for active ingredients in cigarette smoke.