ToxSci Advance Access published online on June 21, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl047
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1 Graduate Program in Cell, Molecular and Developmental Biology, University of California Riverside, Riverside, California 92521
* To whom correspondence should be addressed. Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol and pyrazine) on three types of cultured mammalian cells (HUVEC, HMVEC and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10-18M to 10-2M) of the tested chemicals. After 48 hours, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10-8M to 10-7M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products, and should be subjected to further toxicological testing.
Received April 27, 2006
Accepted June 14, 2006
Neurotoxicology
Cigarette Smoke Toxicants Alter Growth and Survival of Cultured Mammalian Cells
Richard Yu 1,
M. Wu 2,
S. Lin 3,
and
P. Talbot 3 *
2 Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California 92521
3 Graduate Program in Cell, Molecular and Developmental Biology, University of California Riverside, Riverside, California 92521; Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California 92521
P. Talbot, E-mail: talbot{at}ucr.edu
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