Genotoxicity of 10 cigarette smoke condensates in four test systems: comparisons between assays and condensates. 2008

David M DeMarini, and Ramadevi Gudi, and Anna Szkudlinska, and Meena Rao, and Leslie Recio, and Margaret Kehl, and Paul E Kirby, and Gregory Polzin, and Patricia A Richter
Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

The particulate fraction of cigarette smoke, cigarette smoke condensate (CSC), is genotoxic in many short-term in vitro tests and is carcinogenic in rodents. However, no study has evaluated a series of CSCs prepared from a diverse set of cigarettes and produced with different smoking machine regimens in several short-term genotoxicity tests. Here we report on the genotoxicity of 10 CSCs prepared from commercial cigarettes that ranged from ultra-low tar per cigarette (< or =6.5 mg) to full flavor (>14.5 mg) as determined by the Federal Trade Commission (FTC) smoking regimen, a reference cigarette blended to be representative of a U.S. FTC-regimen low-tar cigarette, and experimental cigarettes constructed of single tobacco types. CSCs were tested in the presence of rat liver S9 in the Salmonella plate-incorporation assay using frameshift strains TA98 and YG1041; in micronucleus and comet assays in L5178Y/Tk(+/-) 7.3.2C mouse lymphoma cells, and in CHO-K(1) cells for chromosome aberrations. All 10 CSCs were mutagenic in both strains of Salmonella, and the rank order of their mutagenic potencies was similar. Their mutagenic potencies in Salmonella spanned 7-fold when expressed as rev/mug CSC but 158-fold when expressed as rev/mg nicotine; the range of genotoxic potencies of the CSCs in the other assays was similar regardless of how the data were expressed. All 10 CSCs induced micronuclei with a 3-fold range in their potency. All but one CSC induced DNA damage over a 20-fold range, and all but one CSC induced chromosome aberrations over a 4-fold range. There was no relation among the genotoxic potencies of the CSCs across the assays, and a qualitative advantage of the addition of the other assays to the Salmonella assay was not supported by our findings. Although consideration of nicotine levels may improve the relevance of the quantitative data obtained in the Salmonella and possibly comet assays, compensatory smoking habits and other factors may make the data from the assays used here have qualitative but not quantitative value in assessing risk of cigarette types and cigarette smoking to human health.

UI MeSH Term Description Entries
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012906 Smoke Visible gaseous suspension of carbon and other particulate matter emitted from burning substances.
D014026 Nicotiana A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; the dried leaves of Nicotiana tabacum are used for SMOKING. Tobacco Plant,Nicotiana tabacum,Plant, Tobacco,Plants, Tobacco,Tobacco Plants
D016466 CHO Cells CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells. CHO Cell,Cell, CHO,Cells, CHO
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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