Identification of pyridine compounds in cigarette smoke solution that inhibit growth of the chick chorioallantoic membrane.

Based on prior work, we hypothesized that cigarette smoke contains chemicals that can inhibit growth of the chick chorioallantoic membrane (CAM). In this study, gas chromatography and mass spectrometry were used to identify 12 pyridine derivatives in the inhibitory fractions of smoke eluted from solid phase extraction cartridges. These pyridine derivatives were further studied individually in dose response experiments to determine their effects on CAM growth. A correlation was observed between the functional group substitutions on pyridine and the relative toxicity of each pyridine derivative. In the CAM growth assay, pyridine derivatives with single methyl or single ethyl substitutions had lowest observed adverse effect levels (LOAELs) of 5 x 10(-9) and 5 x 10(-12) M, respectively. Other pyridine derivatives and pyridine itself had LOAELs in the micromolar range. One of the most inhibitory derivatives, 3-ethylpyridine, was studied further and inhibited cell proliferation, as measured by BrdU incorporation. Since 3-ethylpyridine inhibited growth at picomolar doses and is added to consumer products including cosmetics, food, drinks, and tobacco, it will be important to perform further toxicological testing to determine its effect on human health.