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The mutagenic assessment of mainstream cigarette smoke using the Ames assay: a multi-strain approach.

Abstract

Salmonella typhimurium strains TA1535, TA1537, TA97, TA102 and TA104 were assessed for their suitability and use in conjunction with a Vitrocell(®) VC 10 Smoking Robot and 3R4F reference mainstream cigarette smoke. Little information exists on TA97, TA104, TA1535, TA1537 and TA102 using an aerosol 35mm spread-plate format. In this study, TA1535 and TA1537 were considered sub-optimal for use with a scaled-down format, due to low spontaneous revertant numbers (0-5 revertants/plate). In the context of a regulatory environment, TA97 is deemed an acceptable alternative for TA1537 and was therefore selected for whole smoke exposure in this study. However, there is no acceptable alternative for TA1535, therefore this strain was included for whole smoke exposure. TA1535, TA97, TA102 and TA104 were assessed for mutagenic responses following exposure to cigarette smoke at varying concentrations (using diluting airflow rates of 1.0, 4.0, 8.0 and 12.0L/min), and exposure times of 24 and 64min. A positive mutagenic response to cigarette smoke was observed in strain TA104 at both the 24 and 64min time points, in the presence of S-9, at the highest smoke concentration tested (1.0L/min diluting airflow). The three remaining strains were found to be unresponsive to cigarette smoke at all concentrations tested, in the presence and absence of metabolic activation. Cigarette smoke particulate deposition was quantified in situ of exposure using quartz crystal microbalance technology, enabling data to be presented against an associated gravimetric mass (μg/cm(2)). Finally, data obtained in this study were combined with previously published Ames data for TA98, TA100, YG1024, YG1042 and Escherichia coli (WP2 uvrA pKM101), generated using the same 35mm methodology. The combined data-set was used to propose an aerosol testing strategy, based on strain compatibility with the whole smoke aerosol, whilst maintaining the essence of the regulatory guidelines for the standard Ames assay.

Authors+Show Affiliations

British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: David_Thorne@bat.com.Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. Electronic address: Joanne.Kilford@covance.com.Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. Electronic address: Michael.Hollings@covance.com.British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: Annette_Dalrymple@bat.com.Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. Electronic address: Mark.Ballantyne@covance.com.British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: Clive_Meredith@bat.com.British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: Debbie_Dillon@bat.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25868126

Citation

Thorne, David, et al. "The Mutagenic Assessment of Mainstream Cigarette Smoke Using the Ames Assay: a Multi-strain Approach." Mutation Research. Genetic Toxicology and Environmental Mutagenesis, vol. 782, 2015, pp. 9-17.
Thorne D, Kilford J, Hollings M, et al. The mutagenic assessment of mainstream cigarette smoke using the Ames assay: a multi-strain approach. Mutat Res Genet Toxicol Environ Mutagen. 2015;782:9-17.
Thorne, D., Kilford, J., Hollings, M., Dalrymple, A., Ballantyne, M., Meredith, C., & Dillon, D. (2015). The mutagenic assessment of mainstream cigarette smoke using the Ames assay: a multi-strain approach. Mutation Research. Genetic Toxicology and Environmental Mutagenesis, 782, 9-17. https://doi.org/10.1016/j.mrgentox.2015.03.006
Thorne D, et al. The Mutagenic Assessment of Mainstream Cigarette Smoke Using the Ames Assay: a Multi-strain Approach. Mutat Res Genet Toxicol Environ Mutagen. 2015;782:9-17. PubMed PMID: 25868126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The mutagenic assessment of mainstream cigarette smoke using the Ames assay: a multi-strain approach. AU - Thorne,David, AU - Kilford,Joanne, AU - Hollings,Michael, AU - Dalrymple,Annette, AU - Ballantyne,Mark, AU - Meredith,Clive, AU - Dillon,Deborah, Y1 - 2015/03/05/ PY - 2014/11/12/received PY - 2015/02/01/revised PY - 2015/03/03/accepted PY - 2015/4/14/entrez PY - 2015/4/14/pubmed PY - 2015/6/24/medline KW - Ames KW - Dosimetry KW - QCM KW - VC 10 KW - Whole smoke SP - 9 EP - 17 JF - Mutation research. Genetic toxicology and environmental mutagenesis JO - Mutat Res Genet Toxicol Environ Mutagen VL - 782 N2 - Salmonella typhimurium strains TA1535, TA1537, TA97, TA102 and TA104 were assessed for their suitability and use in conjunction with a Vitrocell(®) VC 10 Smoking Robot and 3R4F reference mainstream cigarette smoke. Little information exists on TA97, TA104, TA1535, TA1537 and TA102 using an aerosol 35mm spread-plate format. In this study, TA1535 and TA1537 were considered sub-optimal for use with a scaled-down format, due to low spontaneous revertant numbers (0-5 revertants/plate). In the context of a regulatory environment, TA97 is deemed an acceptable alternative for TA1537 and was therefore selected for whole smoke exposure in this study. However, there is no acceptable alternative for TA1535, therefore this strain was included for whole smoke exposure. TA1535, TA97, TA102 and TA104 were assessed for mutagenic responses following exposure to cigarette smoke at varying concentrations (using diluting airflow rates of 1.0, 4.0, 8.0 and 12.0L/min), and exposure times of 24 and 64min. A positive mutagenic response to cigarette smoke was observed in strain TA104 at both the 24 and 64min time points, in the presence of S-9, at the highest smoke concentration tested (1.0L/min diluting airflow). The three remaining strains were found to be unresponsive to cigarette smoke at all concentrations tested, in the presence and absence of metabolic activation. Cigarette smoke particulate deposition was quantified in situ of exposure using quartz crystal microbalance technology, enabling data to be presented against an associated gravimetric mass (μg/cm(2)). Finally, data obtained in this study were combined with previously published Ames data for TA98, TA100, YG1024, YG1042 and Escherichia coli (WP2 uvrA pKM101), generated using the same 35mm methodology. The combined data-set was used to propose an aerosol testing strategy, based on strain compatibility with the whole smoke aerosol, whilst maintaining the essence of the regulatory guidelines for the standard Ames assay. SN - 1879-3592 UR - https://www.unboundmedicine.com/medline/citation/25868126/The_mutagenic_assessment_of_mainstream_cigarette_smoke_using_the_Ames_assay:_a_multi_strain_approach_ DB - PRIME DP - Unbound Medicine ER -