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Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet
Abstract:
Chronic irradiation of mice with ultraviolet (UV) light produces a systemic alteration of an immunologic nature. This alteration is detectable in mice long before primary skin cancers induced by UV light begin to appear. The alteration results in the failure of UV-irradiated mice to reject highly antigenic, transplanted UV-induced tumors that are rejected by unirradiated syngeneic recipients. The immunologic aspect of this systemic alteration was demonstrated by transferring lymphoid cells from UV-irradiated mice to lethally x-irradiated recipients. These recipeints were unable to resist a later challenge with a syngeneic UV-induced tumor, whereas those given lymphoid cells from normal donors were resistant to tumor growth. Parabiosis of normal mice with UV-irradiated mice, followed by tumor challenge of both parabionts with a UV-induced tumor, resulted in the growth of the challenge tumors in both UV-irradiated and unirradiated mice. Splenic lymphocytes from tumor-implanted UV-treated mice were not cytotoxic in vitro against UV-induced tumors, whereas under identical conditions cells from tumor-implanted, unirradiated mice were highly cytotoxic. Our findings suggest that repeated UV irradiation can circumvent an immunologic mechanism that might otherwise destroy nascent UV-induced primary tumors that are strongly antigenic.
Insights
Chronic ultraviolet (UV) light exposure causes immune suppression in mice, preventing the rejection of UV-induced tumors. This immune alteration occurs before tumors are visible, impacting the body's natural defenses.
Area of Science:
- Immunology
- Dermatology
- Cancer Research
Background:
- Chronic ultraviolet (UV) irradiation induces systemic immunologic alterations in mice.
- These changes are detectable before the onset of UV-induced skin cancers.
- UV-irradiated mice fail to reject highly antigenic, transplanted UV-induced tumors.
Purpose of the Study:
- To investigate the immunologic nature of systemic alterations induced by chronic UV irradiation.
- To determine if UV-induced immune suppression affects the rejection of UV-induced tumors.
- To elucidate the mechanisms by which UV radiation impacts anti-tumor immunity.
Main Methods:
- Transfer of lymphoid cells from UV-irradiated to lethally x-irradiated recipients.
- Parabiosis experiments linking normal and UV-irradiated mice, followed by tumor challenge.
- In vitro cytotoxic assays of splenic lymphocytes against UV-induced tumors.
Main Results:
- Recipients of lymphoid cells from UV-irradiated mice could not resist syngeneic UV-induced tumors.
- Both UV-irradiated and normal parabionts developed tumors after shared exposure.
- Splenic lymphocytes from UV-treated mice showed reduced cytotoxicity against UV-induced tumors compared to controls.
Conclusions:
- Repeated UV irradiation induces a systemic immune suppression that impairs anti-tumor responses.
- This immune evasion mechanism may allow nascent, antigenic UV-induced tumors to survive.
- UV-induced immune tolerance circumvents natural defenses against primary skin tumors.