Citation:

DEMARINI, D. M., R. GUDI, A. SZUDLINSKA, M. RAO, L. RECIO, M. KEHL, P. E. KIRBY, G. POLZIN, AND P. A. RICHTER. GENOTOXICITY OF TEN CIGARETTE SMOKE CONDENSATES IN FOUR TEST SYSTEMS: COMPARISONS BETWEEN ASSAYS AND CONDENSATES. MUTATION RESEARCH. Elsevier Science Ltd, New York, NY, 650(1):15-29, (2008).

Impact/Purpose:

No such comparative study of cigarette smoke condensates has been reported. However, a review of the literature by me for IARC (DeMarini, Mutat. Res. 567:447, 2004) showed that this was an important data gap.

Description:

What is the study?
This the first assessment of a set of cigarette smoke condensates from a range of cigarette types in a variety (4) of short-term genotoxicity assays.
Why was it done?
No such comparative study of cigarette smoke condensates has been reported. However, a review of the literature by me for IARC (DeMarini, Mutat. Res. 567:447, 2004) showed that this was an important data gap.
What is the impact to the field and the agency?
We found that all 10 cigarette smoke condensates were mutagenic in Salmonella and nearly all were mutagenic in of the other 3 assays (DNA damage-comet, micronuclei, and chromosome aberrations in mammalian cells). We concluded that no additional assay beyond the Salmonella assay was necessary for screening cigarette smoke condensates. We also showed that expressing the data on a per-mg-nicotine basis might give a more accurate view of the genotoxic potencies of the condensates. This is because smokers modify their smoking behavior to achieve the equivalent amount of nicotine from a cigarette. These data and considerations may be of value to the Agency when the US EPA considers the effects of environmental tobacco smoke on human health.

Abstract
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 (≤ 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 L578Y/Tk^+/- 7.3.2C mouse lymphoma cells, and in CHO-K₁ 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 8-fold when expressed as rev/μg CSC but 158-fold when expressed as rev/mg nicotine; the range of genotoxic potencies of the CSCs in the other assays were 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 chromosomal 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.

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