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Low-dose-rate gamma radiation aggravates titanium dioxide nanoparticle-induced lung injury in mice

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Abstract

Background

Radiation damage and the cellular response has been studied in various direction, however, the synergic effects of radiation damage with environmental pollution on cells or tissues remained poorly understood. In particular, gene and pathway regulation by low-dose radiation exposure remains unclear. Dust and air pollution in Asian countries contains metal oxide and titanium dioxide nanoparticles (TiO2NPs), which exacerbate respiratory distress.

Objective

To explore the synergic injury of radiation damage with air pollution, we examined the effects of low-dose-rate radiation with TiO2NPs on pulmonary response in mice.

Results

Thirty-six mice (C57bl/6) were divided into six groups: sham, 0.1 Gy, 0.3 Gy, TiO2NPs, TiO2NPs + 0.1 Gy, and TiO2NPs + 0.3 Gy group. Mice were irradiated at a low-dose-rate at a dose of 0.1 Gy (0.182 mGy/h) and 0.3 Gy (0.554 mGy/h) for 24 days and exposed to TiO2NPs by intranasal injection at a dose of 0.1 mg daily for 4 days (from day 21 to 24). The combination of low-dose-rate radiation and TiO2NPs caused significantly more pulmonary inflammation via MAPK phosphorylation in mice than did each stimulus alone.

Conclusion

We conclude that while exposure to each of these two distinct stimuli alone does not cause notable lung damage, they may potentially cause lung damage when combined owing to their synergistic effects. Therefore, we should pay attention to the possible combined effects of low-dose radiation and exposure to TiO2NPs, considering their potential danger in patients with respiratory problems.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Dr. MY Kim and Mr. JK Park for their administrative support.

Funding

This work was supported by a Dongnam Institute of Radiological & Medical Sciences grant funded by the Korean government Ministry of Science and ICT (MSIT) [grant numbers 50492–2016 and 50491–2022] and grants from the National Research Foundation funded by the MSIT [grant numbers NRF-2020M2C8A2069337, NRF-2020R1A2C1004272, and NRF-2020M2C8A2069351].

Author information

Author notes

  1. Sohi Kang and Hae-June Lee have contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, Republic of Korea

    Sohi Kang, Sohee Jeong, Changjong Moon, In-Sik Shin & Joong Sun Kim

  2. Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea

    Hae-June Lee & Yeonghoon Son

  3. Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, Republic of Korea

    Min Ji Bae, Wol Soon Jo & Chang Geun Lee

  4. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju, Republic of Korea

    Jun Hong Park

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  1. Sohi Kang
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Contributions

SK: Formal analysis (lead); Investigation (equal); Writing–original draft (equal); Writing–review and editing (equal). H-JL: Data curation (equal); Formal analysis (equal); Investigation (lead). YS: Formal analysis (equal); Investigation (equal). WSJ: Data curation (equal); Formal analysis (equal). MJB: Methodology (Radiation exposure). JHP: Data curation (equal). SJ: Investigation (Histopathological exam). CM: Data curation (equal); Formal analysis (equal); Investigation (equal); Writing–original draft (lead); Writing–review and editing (equal). CGL and J-SK: Conceptualization (lead); Data curation (equal); Methodology (equal); Writing–original draft (lead); Writing–review and editing (equal).

Corresponding authors

Correspondence to Chang Geun Lee or Joong Sun Kim.

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Conflict of interest

Sohi Kang declares that she has no conflict of interest. Hae-June Lee declares that she has no conflict of interest. Yeonghoon Son declares that he has no conflict of interest. Min Ji Bae declares that she has no conflict of interest. Wol Soon Jo declares that she has no conflict of interest. Jun Hong Park declares that he has no conflict of interest. Sohee Jeong declares that she has no conflict of interest. Changjong Moon declares that he has no conflict of interest. In-Sik Shin declares that he has no conflict of interest. Chang Geun Lee declares that he has no conflict of interest. Joong Sun Kim declares that he has no conflict of interest.

Ethical approval

All animal experiments followed a protocol approved by the Institutional Animal Care and Use Committee of the Dongnam Institute of Radiological & Medical Science (DI-2016–002 and DI-2022–014).

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Kang, S., Lee, HJ., Son, Y. et al. Low-dose-rate gamma radiation aggravates titanium dioxide nanoparticle-induced lung injury in mice. Mol. Cell. Toxicol. 20, 389–398 (2024). https://doi.org/10.1007/s13273-023-00353-2

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