Abstract

The association between ultraviolet (UV) irradiation and skin cancer induction is well known. Recently, UV exposure was associated with the induction of internal lymphoid malignancies in UV-irradiated p53 heterozygous mice. Here we characterize the non-skin cancer that develops in the lymphoid organs of UV-irradiated mice and found that UV exposure promotes the induction of a B-cell lymphoma. p53 heterozygous mice were exposed to UVB irradiation (10KJ/m2; three times a week) supplied by a bank of FS40 sunlamps. After thirty weeks, we collected spleen cells from 5 irradiated mice, prepared single suspensions, pooled the cells and injected 2X106 cells/flank (subcutaneous injection) into Rag2−/−mice. The subcutaneous tumors that developed in the Rag2−/−mice were successfully transplanted into other Rag2−/−mice and adapted to grow in vitro. Flow cytometric analysis indicated that enlarged cells were positive for CD19, B220, IgM, CD24, CD40, B7-1, B7-2, but negative for CD43, BP-1, CD127, CD3, CD4, CD8, CD49b, NK1.1, Thy1.2, Gr-1. This phenotype is compatible with a mature B cell but also express CD5, CD11b, CD117. Immunohistchemical analysis confirmed that the tumor cells were of B-cell origin and southern blot analysis demonstrated rearrangement of Immunoglobulin heavy chain. Chromosomal analysis revealed a translocations, t (14;19). Subcutaneous injection of the tumor cells into Rag2−/− mice resulted in an aggressive tumor that infiltrated into the lymph nodes, the spleen and the bone marrow. After establishing the cell line from this B-cell lymphoma, we transfected GFP by using lentiviral vector to mark and injected into Rag2−/− mice. First, the cells bearing GFP infiltrated into the lymph nodes, and then into the spleen and the bone marrow. We also found that this cell line produced IL-10, which can promote lymphoma growth and can cause systemic immunosuppression (

Masood et al.,
1995
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;
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). The B-cell lymphoma, which grew progressively in immune compromised Rag2−/−mice, was rejected when injected into wild type mice and syngeneic UV-irradiated C57Bl/6 mice. This data indicates that UV induced B-cell lymphoma in p53 heterozygous mice does not express UV common antigen found on UV-induced skin cancer because UV irradiated mice are unable to reject UV induced tumor cells bearing this antigen as previously reported (
Kripke et al.,
1974
J.Natl Cancer Inst.
53
:
1333
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). Since sunlight exposure has been associated with the development of non-Hodgkin’s lymphomas in humans, tumor development in UV-irradiated p53 heterozygous mice may provide a useful animal model for lymphoma development in humans.

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