ArticlePNAS nexus2026
Nicotine metabolites generate craniofacial defects that are worsened by ethanol exposure.
Article in PNAS nexus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
Nicotine and alcohol are two of the most consumed substances among adolescents and adults. There is great concern regarding the deleterious effects of exposure to these substances during pregnancy. Complex interactions between genes and the environment are thought to influence the severity of birth defects and can occur by altering the metabolism of substances. In humans, nicotine is mainly metabolized by CYP2A6 and variants within this enzyme associate with nicotine dependence and metabolism. Previously, we showed that embryonic nicotine exposure reduced the size of craniofacial cartilages in zebrafish. Here, we show that zebrafish metabolize nicotine similarly to humans. We demonstrate that it is not nicotine itself, but nicotine metabolites, particularly 4HPBA followed by nicotine-N'-oxide (NOX), that disrupt craniofacial development. We found that
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