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Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors.

ABSTRACT: Tobacco smoke exposure is associated with neurodevelopmental disorders. We used neuronotypic PC12 cells to evaluate the mechanisms by which tobacco smoke extract (TSE) affects neurodifferentiation. In undifferentiated cells, TSE impaired DNA synthesis and cell numbers to a much greater extent than nicotine alone; TSE also impaired cell viability to a small extent. In differentiating cells, TSE enhanced cell growth at the expense of cell numbers and promoted emergence of the dopaminergic phenotype. Nicotinic receptor blockade with mecamylamine was ineffective in preventing the adverse effects of TSE and actually enhanced the effect of TSE on the dopamine phenotype. A mixture of antioxidants (vitamin C, vitamin E, N-acetyl-l-cysteine) provided partial protection against cell loss but also promoted loss of the cholinergic phenotype in response to TSE. Notably, the antioxidants themselves altered neurodifferentiation, reducing cell numbers and promoting the cholinergic phenotype at the expense of the dopaminergic phenotype, an effect that was most prominent for N-acetyl-l-cysteine. Treatment with methyl donors (vitamin B12, folic acid, choline) had no protectant effect and actually enhanced the cell loss evoked by TSE; they did have a minor, synergistic interaction with antioxidants protecting against TSE effects on growth. Thus, components of tobacco smoke perturb neurodifferentiation through mechanisms that cannot be attributed to the individual effects of nicotine, oxidative stress or interference with one-carbon metabolism. Consequently, attempted amelioration strategies may be partially effective at best, or, as seen here, can actually aggravate injury by interfering with normal developmental signals and/or by sensitizing cells to TSE effects on neurodifferentiation.

SUBMITTER: Slotkin TA

PROVIDER: S-EPMC4466202 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors.

Slotkin Theodore A TA Skavicus Samantha S Card Jennifer J Levin Edward D ED Seidler Frederic J FJ

Toxicology 20150417

Tobacco smoke exposure is associated with neurodevelopmental disorders. We used neuronotypic PC12 cells to evaluate the mechanisms by which tobacco smoke extract (TSE) affects neurodifferentiation. In undifferentiated cells, TSE impaired DNA synthesis and cell numbers to a much greater extent than nicotine alone; TSE also impaired cell viability to a small extent. In differentiating cells, TSE enhanced cell growth at the expense of cell numbers and promoted emergence of the dopaminergic phenotyp ...[more]

PMID: 25891525

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Project description:BackgroundAirports may represent significant sources of secondhand smoke (SHS) exposure for both travelers and employees. While previously common smoking rooms have largely disappeared from US airports, smoking continues to occur outdoors at terminal entrances. SHS may be especially high at arrival areas, since they oftentimes are partially enclosed by overhead departures, creating stagnant microenvironments. This study assessed particulate matter <2.5 microns in diameter (PM2.5), a common surrogate for SHS, at airport terminal locations to evaluate both outdoor exposure risk and possible indoor drift of SHS from outdoor sources.MethodsA convenience sample of nine airport terminal arrival areas in the US state of Florida was surveyed between February and July 2018. PM2.5 levels were assessed outdoors and indoors at terminal entrances and at control areas far into terminal interiors. We also examined the impact of smoking location on SHS exposure by correlating cigarette and passing vehicle counts with PM2.5 levels at terminals with contrasting proximity of designated smoking locations to terminal entrances.ResultsAlthough outdoor PM2.5 levels (mean 17.9, SD 6.1 µg/m3) were significantly higher than indoors (p < 0.001), there was no difference between indoor areas directly inside terminal entrances and areas much further interior (mean 8.8, SD 2.6 vs mean 8.5, SD 3.0 µg/m3, p=0.49). However, when smoking areas were in close proximity to terminal entrances, the number of lit cigarettes and vehicular traffic per minute predicted 70% of the variance of PM2.5 levels (p < 0.001), which was attributable mostly to the cigarette number (β = 0.83; 95% CI (0.55 to 1.11); p < 0.001). This effect was not observed at smoking areas further away.ConclusionPM2.5 data did not suggest indoor drift from outside smoking. Nevertheless, absolute exposure outdoors was high and correlated with the location of designated smoking areas. Further studies are needed to examine the effect of microclimate formation on exposure risk.

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Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors.

Publications

Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors.

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