title: Genetic toxicology and toxicogenomic analysis of three cigarette smoke condensates in vitro reveals few differences among full-flavor, blonde, and light products.
abstract: Cigarette smoking leads to various detrimental health outcomes. Tobacco companies produce different brands of cigarettes that are marketed as reduced harm tobacco products. Early examples included "light" cigarettes, which differ from regular cigarettes due to filter ventilation and/or differences in chemical constituents. In order to establish baseline similarities and differences among different tobacco brands available in Canada, the present study examined the cytotoxicity, mutagenicity, clastogenicity, and gene expression profiles of cigarette smoke condensate (CSC) from three tobacco products, encompassing a full-flavor, blonde, and "light" variety. Using the Salmonella mutagenicity assay, we confirmed that the three CSCs are mutagenic, and that the potency is related to the presence of aromatic amines. Using the Muta™Mouse FE1 cell line we determined that the CSCs were clastogenic and cytotoxic, but nonmutagenic, and the results showed few differences in potencies among the three brands. There were no clear brand-specific changes in gene expression; each brand yielded highly similar expression profiles within a time point and concentration. The molecular pathways and biological functions affected by exposure included xenobiotic metabolism, oxidative stress, DNA damage response, cell cycle arrest and apoptosis, as well as inflammation. Thus, there was no appreciable difference in toxicity or gene expression profiles between regular brands and products marketed as "light," and hence no evidence of reduced harm. The work establishes baseline CSC cytotoxicity, mutagenicity, and expression profiles that can be used as a point of reference for comparison with data generated for products marketed as reduced harm and/or modified risk tobacco products.
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada. Carole.Yauk@hc-sc.gc.ca
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Julie K
authors.initials: JK
authors.lastname: Buick
authors.forename: Guosheng
authors.initials: G
authors.lastname: Chen
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Maertens
authors.forename: Sabina
authors.initials: S
authors.lastname: Halappanavar
authors.forename: Paul A
authors.initials: PA
authors.lastname: White
mesh_terms: D000588:Amines / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D002170:Canada; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D066298:In Vitro Techniques; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012475:Salmonella / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects / Q000032:analysis*; D012907:Smoking / Q000009:adverse effects*; D043922:Toxicogenetics / Q000379:methods; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D000588:Amines; D012906:Smoke; D001616:beta-Galactosidase