title: Mass Spectrometric Approaches to the Identification of Potential Ingredients in Cigarette Smoke Causing Cytotoxicity.
abstract: Cigarette smoke contains many harmful chemicals that contribute to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease, cancer, and cardiovascular disease. Many studies have been done to identify cytotoxic chemicals in cigarette smoke and elucidate the onset of the above-mentioned diseases caused by smoking. However, definitive mechanisms for cigarette smoke toxicity remain unknown. As candidates for cytotoxic chemicals, we have recently found methyl vinyl ketone (MVK) and acetic anhydride in nicotine/tar-free cigarette smoke extract (CSE) using L-tyrosine (Tyr), an amino acid with highly reactive hydroxyl group. The presence of MVK and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). We also found new reaction products formed in B16-BL6 mouse melanoma (B16-BL6) cells treated with CSE using LC/MS. These were identified as glutathione (GSH) conjugates of α,β-unsaturated carbonyl compounds, MVK, crotonaldehyde (CA), and acrolein (ACR), by the mass value and product ion spectra of these new products. ACR and MVK are type-2 alkenes, which are well known as electron acceptors and form Michael-type adducts to nucleophilic side chain of amino acids on peptides. These α,β-unsaturated carbonyl compounds may have a key role in CSE-induced cell death.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University.
authors.forename: Shizuyo
authors.initials: S
authors.lastname: Horiyama
authors.forename: Masaru
authors.initials: M
authors.lastname: Kunitomo
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D000089:Acetic Anhydrides / Q000032:analysis* / Q000633:toxicity; D000818:Animals; D002074:Butanones / Q000032:analysis* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D008546:Melanoma, Experimental; D051379:Mice; D012906:Smoke / Q000009:adverse effects / Q000032:analysis*; D062789:Tobacco Products; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D000089:Acetic Anhydrides; D002074:Butanones; D012906:Smoke; C031800:acetic anhydride; D014443:Tyrosine; C057920:3-buten-2-one; D005978:Glutathione