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Few X-ray and PUVA treatments accelerate photocarcinogenesis in hairless mice

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Abstract

PUVA is a treatment that combines oral methoxypsoralen (8-MOP) with ultraviolet radiation A (UVA). It is used for severe psoriasis and the early stages of T-cell lymphoma. X-rays are an effective treatment for skin cancers. Both treatments are in higher doses used to treat skin malignancies and simultaneously increase the risk of keratinocyte cancer. The main objective of this study was to test whether a few PUVA or X-ray treatments could delay the development of ultraviolet radiation (UVR)-induced skin tumors in a well-established hairless mouse model. Three groups of immunocompetent mice (total, N = 75) were included in the study. All groups were UVR-exposed during the study period. In addition, one group was treated with PUVA and another group was treated with X-rays at days 45, 52, 90 and 97. A control group was treated with UVR only. We recorded when the first, second and third skin tumors were induced in each mouse. Skin tumors developed significantly earlier in both the PUVA and X-ray groups (median, 188 days) than in the control mice (median, 215 days; p < 0.001). Therefore, a few X-ray and PUVA treatments both significantly accelerated the development of skin tumors in hairless mice, compared to UVR controls. Neither treatment showed a delay of UVR-induced skin tumors and caution should be exercised before applying these treatments to sun-damaged skin.

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Data availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

The authors extend their gratitude to the nurses from the Department of Dermatology D41 for helping with the X-ray treatments and M.Sc. E.E. Jakob Heydenreich for recording the spectrum of the UVA source. This work was executed as a part of the Danish Research Center for Skin Cancer and the Skin Cancer Innovation Clinical Academic Group (SCIN CAG), Greater Copenhagen Health Science Partners (GCHSP).

Funding

The research was supported by Copenhagen University Hospital, Bispebjerg and Kgl. Hofbundtmager Aage Bangs Foundation. C.M.L is supported by an unrestricted grant from the Lundbeck Foundation (R307-2018-3318).

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Authors and Affiliations

  1. Department of Dermatology, D92, Copenhagen University Hospital, Nielsine Nielsensvej 17, Entrance 9, 2400, Copenhagen, Denmark

    Catharina M. Lerche, Rami Nabil Al-Chaer, Martin Glud, Peter Alshede Philipsen & Hans Christian Wulf

  2. Department of Pharmacy, University of Copenhagen, Copenhagen, Universitetsparken 2, 2100, Denmark

    Catharina M. Lerche

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  1. Catharina M. Lerche
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Contributions

Conceptualization: HCW, PAP, and CML; methodology: HCW, PAP, and CML; validation: MG; formal analysis: PAP, CML, and MG; investigation: CML; resources: HCW and CML; data curation: RNA; writing—original draft preparation: RNA and CML; writing—review and editing: HCW, RNA, MG, PAP, and CML; visualization: RNA and CML; supervision: HCW and CML; project administration: CML; funding acquisition: CML. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Catharina M. Lerche.

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The authors have no conflicts of interest to declare that are relevant to the content of this article.

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All protocols were approved by the Danish Animal Experiments Inspectorate (permit number 2014-15-0201-00096) and our Institutional Animal Care and Use Committee.

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Lerche, C.M., Al-Chaer, R.N., Glud, M. et al. Few X-ray and PUVA treatments accelerate photocarcinogenesis in hairless mice. Photochem Photobiol Sci 20, 1299–1307 (2021). https://doi.org/10.1007/s43630-021-00105-y

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  • DOI: https://doi.org/10.1007/s43630-021-00105-y

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