title: Mutagenicity of 11 cigarette smoke condensates in two versions of the mouse lymphoma assay.
abstract: Cigarette smoke condensate (CSC) is genotoxic in nearly all assays in which it has been tested. In this study, we investigated the mutagenicity of 11 CSCs using the microwell and soft-agar versions of the mouse lymphoma assay (MLA). These CSCs were prepared from commercial or experimental cigarettes, 10 of them were produced using International Organisation for Standardisation (ISO) conditions and one CSC was generated using intense Massachusetts Department of Public Health (MDPH) conditions. In the presence of rat liver S9, the L5178Y/Tk(+/-) mouse lymphoma cells were treated with 11 CSCs at different concentrations (25-200 μg/ml) for 4 h. All CSCs resulted in dose-dependent increases of both cytotoxicity and mutagenicity in both versions of the MLA. The mutagenic potencies of the CSCs were calculated as mutant frequency per microgram CSC from the slope of the linear regression of the dose-response curves and showed no correlations with the tar yield of the cigarette or nicotine concentrations of the CSCs. Comparing two CSCs produced from the same commercial cigarettes using two different smoking conditions, the one generated under ISO conditions was more mutagenic than the other generated under intense conditions on a per microgram CSC basis. We also examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for the mutants induced by 11 CSCs. The most common type of mutation observed was LOH with chromosome damage spanning less than ∼34 Mbp. These results indicate that the MLA identifies different genotoxic potencies among a variety of CSCs and that the results from both versions of the assay are comparable.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Guo
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Verkler
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Richter
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Polzin
authors.forename: Martha M
authors.initials: MM
authors.lastname: Moore
authors.forename: Nan
authors.initials: N
authors.lastname: Mei
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008223:Lymphoma / Q000473:pathology; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000032:analysis; D013937:Thymidine Kinase / Q000235:genetics; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*
chemical_list: D009153:Mutagens; D012906:Smoke; D013937:Thymidine Kinase