title: 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: British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: David_Thorne@bat.com.
authors: David
authors: D
authors: Thorne
authors: Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. Electronic address: Joanne.Kilford@covance.com.
authors: Joanne
authors: J
authors: Kilford
authors: Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. Electronic address: Michael.Hollings@covance.com.
authors: Michael
authors: M
authors: Hollings
authors: British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: Annette_Dalrymple@bat.com.
authors: Annette
authors: A
authors: Dalrymple
authors: Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire HG3 1PY, UK. Electronic address: Mark.Ballantyne@covance.com.
authors: Mark
authors: M
authors: Ballantyne
authors: British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: Clive_Meredith@bat.com.
authors: Clive
authors: C
authors: Meredith
authors: British American Tobacco, Group R&D, Southampton, Hampshire SO15 8TL, UK. Electronic address: Debbie_Dillon@bat.com.
authors: Deborah
authors: D
authors: Dillon
mesh_terms: D000336:Aerosols / Q000633:toxicity; D000393:Air Pollutants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D009152:Mutagenicity Tests / Q000379:methods*; D009154:Mutation; D012486:Salmonella typhimurium / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D012906:Smoke; D013045:Species Specificity; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D012906:Smoke
keywords: Ames; Dosimetry; QCM; VC 10; Whole smoke