UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53

Weidong Jiang, Honnavara N. Ananthaswamy, H. Konrad Muller, Allal Ouhtit, Svetlana Bolshakov, Stephen E. Ullrich, Adel K. El-Naggar, Margaret L. Kripke

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Abstract

Epidemiological studies have suggested an association between exposure to solar UV radiation and the incidence of lymphoid malignancies, which has increased substantially worldwide during the last two decades. Findings from animal studies have raised the question of whether UV radiation might influence the development of lymphoid malignancies by means of its immunosuppressive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen, p53 heterozygous mice with only one copy of the wild-type allele also develop lymphoid malignancies, but with a much lower frequency and a long latent period. In our study using mice of the C57BL/6 background, only one of the unirradiated mice lacking one copy of p53 (p53+/-) spontaneously developed a lymphoid tumor (6%), whereas 88% of UV-irradiated p53+/- mice developed lymphoid tumors in the spleen or liver. None of the control or UV-irradiated p53 wild-type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53-/-) rapidly developed thymic lymphomas and/or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune responses of the mice to contact sensitization were identical and were suppressed to the same extent by UV irradiation regardless of the genotype. These results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in addition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not account for the accelerated development of lymphoid tumors in UV-irradiated p53+/- mice, deletions in the p16INK4a gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neoplasms in genetically susceptible mice and support the hypothesis that extensive sunlight exposure contributes to the induction of lymphoma in humans.

Original languageEnglish
Pages (from-to)9790-9795
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number17
DOIs
Publication statusPublished - Aug 14 2001

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Lymphatic Irradiation
Neoplasms
Spleen
Lymphoma
Radiation
p16 Genes
T-Lymphocytes
Sunlight
Loss of Heterozygosity
Liver
Radiation Effects
Immunosuppressive Agents
Inbred C57BL Mouse

Keywords

  • Immune suppression
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53. / Jiang, Weidong; Ananthaswamy, Honnavara N.; Muller, H. Konrad; Ouhtit, Allal; Bolshakov, Svetlana; Ullrich, Stephen E.; El-Naggar, Adel K.; Kripke, Margaret L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 17, 14.08.2001, p. 9790-9795.

Research output: Contribution to journalArticle

Jiang, W, Ananthaswamy, HN, Muller, HK, Ouhtit, A, Bolshakov, S, Ullrich, SE, El-Naggar, AK & Kripke, ML 2001, 'UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9790-9795. https://doi.org/10.1073/pnas.171066498
Jiang, Weidong ; Ananthaswamy, Honnavara N. ; Muller, H. Konrad ; Ouhtit, Allal ; Bolshakov, Svetlana ; Ullrich, Stephen E. ; El-Naggar, Adel K. ; Kripke, Margaret L. / UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 17. pp. 9790-9795.
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abstract = "Epidemiological studies have suggested an association between exposure to solar UV radiation and the incidence of lymphoid malignancies, which has increased substantially worldwide during the last two decades. Findings from animal studies have raised the question of whether UV radiation might influence the development of lymphoid malignancies by means of its immunosuppressive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen, p53 heterozygous mice with only one copy of the wild-type allele also develop lymphoid malignancies, but with a much lower frequency and a long latent period. In our study using mice of the C57BL/6 background, only one of the unirradiated mice lacking one copy of p53 (p53+/-) spontaneously developed a lymphoid tumor (6{\%}), whereas 88{\%} of UV-irradiated p53+/- mice developed lymphoid tumors in the spleen or liver. None of the control or UV-irradiated p53 wild-type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53-/-) rapidly developed thymic lymphomas and/or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune responses of the mice to contact sensitization were identical and were suppressed to the same extent by UV irradiation regardless of the genotype. These results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in addition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not account for the accelerated development of lymphoid tumors in UV-irradiated p53+/- mice, deletions in the p16INK4a gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neoplasms in genetically susceptible mice and support the hypothesis that extensive sunlight exposure contributes to the induction of lymphoma in humans.",
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AU - Ouhtit, Allal

AU - Bolshakov, Svetlana

AU - Ullrich, Stephen E.

AU - El-Naggar, Adel K.

AU - Kripke, Margaret L.

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N2 - Epidemiological studies have suggested an association between exposure to solar UV radiation and the incidence of lymphoid malignancies, which has increased substantially worldwide during the last two decades. Findings from animal studies have raised the question of whether UV radiation might influence the development of lymphoid malignancies by means of its immunosuppressive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen, p53 heterozygous mice with only one copy of the wild-type allele also develop lymphoid malignancies, but with a much lower frequency and a long latent period. In our study using mice of the C57BL/6 background, only one of the unirradiated mice lacking one copy of p53 (p53+/-) spontaneously developed a lymphoid tumor (6%), whereas 88% of UV-irradiated p53+/- mice developed lymphoid tumors in the spleen or liver. None of the control or UV-irradiated p53 wild-type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53-/-) rapidly developed thymic lymphomas and/or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune responses of the mice to contact sensitization were identical and were suppressed to the same extent by UV irradiation regardless of the genotype. These results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in addition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not account for the accelerated development of lymphoid tumors in UV-irradiated p53+/- mice, deletions in the p16INK4a gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neoplasms in genetically susceptible mice and support the hypothesis that extensive sunlight exposure contributes to the induction of lymphoma in humans.

AB - Epidemiological studies have suggested an association between exposure to solar UV radiation and the incidence of lymphoid malignancies, which has increased substantially worldwide during the last two decades. Findings from animal studies have raised the question of whether UV radiation might influence the development of lymphoid malignancies by means of its immunosuppressive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen, p53 heterozygous mice with only one copy of the wild-type allele also develop lymphoid malignancies, but with a much lower frequency and a long latent period. In our study using mice of the C57BL/6 background, only one of the unirradiated mice lacking one copy of p53 (p53+/-) spontaneously developed a lymphoid tumor (6%), whereas 88% of UV-irradiated p53+/- mice developed lymphoid tumors in the spleen or liver. None of the control or UV-irradiated p53 wild-type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53-/-) rapidly developed thymic lymphomas and/or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune responses of the mice to contact sensitization were identical and were suppressed to the same extent by UV irradiation regardless of the genotype. These results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in addition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not account for the accelerated development of lymphoid tumors in UV-irradiated p53+/- mice, deletions in the p16INK4a gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neoplasms in genetically susceptible mice and support the hypothesis that extensive sunlight exposure contributes to the induction of lymphoma in humans.

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