Scholarlink

<p>Cigarette smoke contains over 5000 compounds, including polycyclic aromatic hydrocarbons, which induce cytochrome P450 (CYP) enzymes, particularly CYP1A1 and CYP1A2. Therefore, smoking significantly alters drug metabolism and can reduce therapeutic efficacy. To investigate tissue-specific CYP enzyme induction by cigarette smoke extract (CSE), a previously established hepatic in vitro smoke induction model was expanded to include human intestinal organoids and lung cell models. CYP1A1, CYP1A2, and CYP3A4 mRNA expression and CYP1A1 and CYP1A enzyme activity were quantified following CSE exposure. CYP1A1 mRNA expression and enzyme activity were robustly induced in all tissues and donors (up to 77-fold and 212-fold respectively). CYP1A2 mRNA and CYP1A enzyme activity were induced in liver and intestine (up to 13-fold) but were only weakly detectable in lung. CYP3A4 induction was exclusively observed in liver (up to 16-fold). Comparison of F<sub>2</sub>- and E<sub>max</sub>-values of concentration-dependent induction across all models revealed that intestinal cells showed significantly lower values of CYP1A1 induction than liver cells. Other comparisons were non-significant. Inter-donor variability was visible across all cell models, CYP enzymes and tissue types (57–82% CV). This reflects physiological inter-individual variability, supporting the conclusion that these single-cell models capture donor-specific differences. Conclusively, it was shown that extrahepatic metabolism is altered by CSE and that considering tissue-specific CYP enzyme induction may be beneficial in clinical pharmacology to optimize drug efficacy and safety in smoking populations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Extending a liver-based model to lung and intestine: a comparative study of CYP1A1 and CYP1A2 induction by cigarette smoke in human in vitro models

  • 期刊论文

  • 发表日期：

    2026年2月17日

查看全文
  • Ann-Kathrin Lenich,
  • Wataru Kishimoto,
  • Hiroshi Nakase,
  • Tatsuya Inui,
  • Hiroyuki Mizuguchi,
  • Stephanie Ruez

摘要

Cigarette smoke contains over 5000 compounds, including polycyclic aromatic hydrocarbons, which induce cytochrome P450 (CYP) enzymes, particularly CYP1A1 and CYP1A2. Therefore, smoking significantly alters drug metabolism and can reduce therapeutic efficacy. To investigate tissue-specific CYP enzyme induction by cigarette smoke extract (CSE), a previously established hepatic in vitro smoke induction model was expanded to include human intestinal organoids and lung cell models. CYP1A1, CYP1A2, and CYP3A4 mRNA expression and CYP1A1 and CYP1A enzyme activity were quantified following CSE exposure. CYP1A1 mRNA expression and enzyme activity were robustly induced in all tissues and donors (up to 77-fold and 212-fold respectively). CYP1A2 mRNA and CYP1A enzyme activity were induced in liver and intestine (up to 13-fold) but were only weakly detectable in lung. CYP3A4 induction was exclusively observed in liver (up to 16-fold). Comparison of F2- and Emax-values of concentration-dependent induction across all models revealed that intestinal cells showed significantly lower values of CYP1A1 induction than liver cells. Other comparisons were non-significant. Inter-donor variability was visible across all cell models, CYP enzymes and tissue types (57–82% CV). This reflects physiological inter-individual variability, supporting the conclusion that these single-cell models capture donor-specific differences. Conclusively, it was shown that extrahepatic metabolism is altered by CSE and that considering tissue-specific CYP enzyme induction may be beneficial in clinical pharmacology to optimize drug efficacy and safety in smoking populations.