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<p>The industrial uses of titanium dioxide (TiO<sub>2</sub>) are extensive, with pigment grades (particle size &gt; 100&#xa0;nm) being the most common forms produced. Nanoforms (particle size &lt; 100&#xa0;nm) of TiO<sub>2</sub> (e.g., P25) are also produced for specialist applications such as photocatalysts. P25 induced inflammatory and carcinogenic lung responses in rats at high exposure doses inducing lung overload. We previously identified an in vitro transcriptomic signature (18 genes) associated with overload of P25, in rat alveolar macrophages. The objective of the present study was to determine whether this signature also applies to other, more commonly used pigment grades of TiO<sub>2</sub>. Using high-throughput sequencing, we examined the transcriptomic responses of three TiO<sub>2</sub> grades (the photocatalyst P25 and two pigment grades, G3-1 and Bayertitan T) in primary rat alveolar macrophages exposed in vitro at non-overload (4&#xa0;µg/mL for P25; 2&#xa0;µg/mL for G3-1 and Bayertitan T) or overload (40&#xa0;µg/mL for P25; 20&#xa0;µg/mL for G3-1 and Bayertitan T) doses. At an equivalent internalized volume of particles, the response to P25 overload was significantly higher than those to pigment particles. However, a consistent modulation of the 18-gene signature was observed across all three TiO<sub>2</sub> grades, albeit with a markedly lower magnitude of response for the pigment particles. Although the gene signature of particle overload in rat alveolar macrophages seems to apply across different TiO<sub>2</sub> particle grades, our results suggest that unrealistic and extreme exposure concentrations to the pigment TiO<sub>2</sub> particles would be required to induce in vivo toxicity similar to that observed with P25 particles.</p>

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Transcriptomic profile of TiO2 particle overload in rat alveolar macrophages: examining responses between P25 and two pigment grade particles in vitro

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月21日

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  • Laeticia Perez,
  • Jérôme Ambroise,
  • Bertrand Bearzatto,
  • Yousof Yakoub,
  • Mihaly Palmai-Pallag,
  • Caroline Bouzin,
  • Laurence Ryelandt,
  • Cristina Pavan,
  • François Huaux,
  • Dominique Lison

摘要

The industrial uses of titanium dioxide (TiO2) are extensive, with pigment grades (particle size > 100 nm) being the most common forms produced. Nanoforms (particle size < 100 nm) of TiO2 (e.g., P25) are also produced for specialist applications such as photocatalysts. P25 induced inflammatory and carcinogenic lung responses in rats at high exposure doses inducing lung overload. We previously identified an in vitro transcriptomic signature (18 genes) associated with overload of P25, in rat alveolar macrophages. The objective of the present study was to determine whether this signature also applies to other, more commonly used pigment grades of TiO2. Using high-throughput sequencing, we examined the transcriptomic responses of three TiO2 grades (the photocatalyst P25 and two pigment grades, G3-1 and Bayertitan T) in primary rat alveolar macrophages exposed in vitro at non-overload (4 µg/mL for P25; 2 µg/mL for G3-1 and Bayertitan T) or overload (40 µg/mL for P25; 20 µg/mL for G3-1 and Bayertitan T) doses. At an equivalent internalized volume of particles, the response to P25 overload was significantly higher than those to pigment particles. However, a consistent modulation of the 18-gene signature was observed across all three TiO2 grades, albeit with a markedly lower magnitude of response for the pigment particles. Although the gene signature of particle overload in rat alveolar macrophages seems to apply across different TiO2 particle grades, our results suggest that unrealistic and extreme exposure concentrations to the pigment TiO2 particles would be required to induce in vivo toxicity similar to that observed with P25 particles.