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Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones

Oncogene volume 22, pages 6369–6376 (2003)Cite this article

Abstract

Chronic irradiation of human or murine epidermis with ultraviolet B (UVB) induces clones of p53-mutant keratinocytes. Clones precede and parallel the induction of carcinomas, suggesting that they are an early stage of UVB carcinogenesis. In the absence of UVB, these clones rapidly regress. For UVB-induced murine skin tumors and papillomas, regression is known to involve antigen-specific immunity. To determine whether antigen-specific immunity influences the creation, expansion, or regression of p53-mutant clones, we studied Rag1 knockout mice deficient in the recombination activating gene 1 required for development of B, αβT, γδT, and natural killer T cells. Since tissue homeostasis could affect proliferation or persistence of clones, we also examined the effect of Rag1 on UVB-induced hyperplasia and apoptosis. Mice were irradiated with UVB daily for 7–11 weeks to create p53-mutant clones, and then retained in the absence of UV. After UV ended, epidermal thickness decreased and p53-mutant clones observed in the epidermal sheets regressed, with no significant differences between Rag1−/− and wild type. During the initial chronic UVB irradiation, increasing irradiation time increased both the number and size of p53-mutant clones, with no significant difference between genotypes. We conclude that antigen-specific immunity is not involved in the initiation, expansion, or acute regression of p53-mutant clones.

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Abbreviations

MED, minimal esythermal dose; NK:

natural killer

PBS:

phosphate-buffered saline

Rag1 :

recombination activating gene 1

SBC:

sunburn cell

UVB:

ultraviolet B (280–320 nm)

XPA:

xeroderma pigmentosum complementation group A

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Acknowledgements

We are grateful to C Adrada for technical assistance, R Tarone for statistical analysis, and D Schatz, R Tigelaar, and J McNiff for advice on immunology and dermatopathology. This work was supported by NIH Grant CA78735 to DEB.

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Authors and Affiliations

  1. Department of Therapeutic Radiology, Yale University, New Haven, CT, USA

    Éva Remenyik, Norbert M Wikonkál, Wengeng Zhang, Vipin Paliwal & Douglas E Brash

  2. Department of Genetics, Yale University, New Haven, CT, USA

    Éva Remenyik, Norbert M Wikonkál, Wengeng Zhang, Vipin Paliwal & Douglas E Brash

  3. Yale Cancer Center, Yale University, New Haven, CT, USA

    Éva Remenyik, Norbert M Wikonkál, Wengeng Zhang, Vipin Paliwal & Douglas E Brash

  4. Department of Dermatology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Éva Remenyik & Norbert M Wikonkál

  5. Department of Dermatology, Semmelweis University School of Medicine, Budapest, 1085, Hungary

    Norbert M Wikonkál

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  1. Éva Remenyik
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Correspondence to Douglas E Brash.

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Remenyik, É., Wikonkál, N., Zhang, W. et al. Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones. Oncogene 22, 6369–6376 (2003). https://doi.org/10.1038/sj.onc.1206657

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