Phorol-hernisrry and Pkorobiology, 1976, Vol. 24, pp. 599-600.

Pergamon Press. Printed

ill

Great Britain

RESEARCH NOTE

TARGET ORGAN FOR A SYSTEMIC EFFECT OF ULTRAVIOLET RADIATION MARGARET L. KRIPKE Basic Research Program, NCI Frederick Cancer Research Center, Frederick, MD 21701, U.S.A. (Received 10 May 1976; accepted 30 June 1976)

INTRODUCTION

Recent work from this laboratory demonstrated that chronic treatment with UV radiation brings about a systemic alteration in inbred mice. One consequence of this alteration is the abrogation of host resistance against UV-light-induced skin cancer (Kripke and Fisher, 1976). The mechanism of this suppression is still undetermined. However, studies on the immunologic responsiveness of UV-irradiated mice suggest that the abrogation of host resistance to UV-induced tumors is not brought about by direct inactivation of immunocompetent cells (Kripke and Fisher, 1976; Kripke, unpublished data). This implies that UV light acts in an indirect way to induce the systemic change. In order to study how UV light exerts its effect, it was desirable to know whether the effective radiation entered the host through the skin or through the eyes. A visual requirement would suggest a pinealhormonal mechanism, whereas a topical requirement might imply the production of chemical mediators or the destruction of biochemical regulators in the skin. These experiments demonstrate that the suppression of resistance to UV-induced tumor growth is effected by UV light incident upon the skin, rather than the retina.

shaved with electric clippers (Oster, No. 40 blade) once per week. Dorsal hair was removed from the base of the tail to the nape of the neck and to the lateral mid-lines. This treatment regimen produces skin tumors on the ears and backs of the mice in an average of 32 weeks (range = 2 2 4 2 weeks). Following tumor challenge, UV treatment continued until termination of the experiment. Tumor challenge. The tumor used for challenge was a fibrosarcoma induced in a C3H/HeN(MTV-) mouse by the UV-treatment regimen described above. Since it rarely grows in normal syngeneic mice, the tumor was maintained by serial passage in syngeneic mice immunosuppressed by adult thymectomy and whole body X-irradiation (450 R). For challenge, the tumors were excised, cut into 1 mm3 fragments and transplanted subcutaneously with a trocar on the ventral (non-UV-irradiated) side of the test animals. The mice were inspected once a week for growth of the tumor implants and tumor sizes were recorded. Progressively growing tumors are defined as thosc reaching a sufficient size to induce morbidity or mortality in a recipient. Mice that did not develop tumors were observed until all tumor-bearers died from progressive tumor growth (at least 6 weeks). Enucleation. The mice were anesthetized with sodium pentobarbital. A slip-knot loop in the center of a suture thread was placed around the eyeball and pulled taut, severing the optic nerve. The eye was removed and the eyelids were sutured closed to prevent infection of the orbit. Ultraviolet treatment of these mice was started 2 weeks after surgery. RESULTS AND DISCUSSlON

MATERIALS AND METHODS

The first experiment attempted to test whether or

Mice. Specific-pathogen-free mice of the inbred strain not the systemic alteration was produced by UV light C3H/HeN(MTV-) were obtained from the Frederick Cancer Research Center Animal Production Facility. The entering via the skin. Mice that were U V treated and mice were 6 to 8 weeks old at the start of the experiments. either shaved once a week with electric clippers or UVirradiution. The light source was a bank of 6 Westinghouse FS40 Sunlamps, which delivered an average dose Table 1. Effect of hair clipping on UV-induced susceptibirate of 2.8 J/m2/s over the wavelength range of 28@-340 lity to tumor challenge nm. (This range includes approximately 80% of the total energy output of the lamps.) Measurements were made Weeks of UV treatment with an International Light Spectroradiometer System (IL Treatment prior to challenge 700/760/780) containing a PM270D-CM149 detector with Hair uv a spectral range of 240-810 nm. The mice were housed 8 14 clipped radiation ~ _ _ _ 5 per cage on a shelf 20 cm below the fluorescent bulbs. The bulbs were turned on for 1 h, 3 times per week (Mon., 1/10 oj1o Wed., and Fri.), and the cage order was systematically 10/10 9/10 rotated prior to each treatment to compensate for the un5/10 9/10 even lamp output along the shelf. Room lights were on Number of mice with progressively growing tumor/ an automated cycle for 12 h of light and 12 h of dark. Unless otherwise indicated, the irradiated mice were number challenged. 599

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600

MARGARET L. KRIPKE

Table 2. Effect of blindness on UV-induced susceptibility did contribute to the abrogation of tumor rejection, to tumor challenge or the hair was not as effective a skin shield as was expected. Treatments To distinguish between these possibilities, a second UV radiation* Tumor experiment was performed to test the tumor susceptiEnucleation (9 weeks) incidencet bility of mice whose eyes were removed prior to UV +0/10 treatment. The data are summarized in Table 2. Mice ++ 8/9 that were enucleated, but not UV treated rejected the + 12/14 tumor implants, showing that the surgical procedure *UV treated for 60 min, 3 times per week, and shaved did not affect tumor rejection. Mice that were shaved once a week for 9 weeks prior to tumor challenge. and UV irradiated were susceptible to tumor chal?Number of mice with progressively growing tumor/ lenge, regardless of their visual status. This demonnumber challenged. strates that light entering via the optic pathway is not responsible for the effect of UV radiation on left with their hair intact were tested for their ability tumor rejection. Therefore, the systemic effect of UV to reject a transplanted UV-induced tumor. The hair irradiation must be mediated by light directed at the on the unclipped mice was expected to prevent the skin. It is also apparent that even though hair promajority of the UV light from reaching the skin, tects the underlying skin from the direct carcinogenic although the ears and tail were still exposed. effects of UV exposure, it only provides a sufficient The data in Table 1 show that untreated control shield to retard, but not prevent, the induction of the mice generally rejected the transplanted tumor, while systemic alteration. hair clipped, irradiated mice were highly susceptible to tumor challenge. A shielding effect of hair was seen after 8 weeks of UV treatment, when only half of the mice were susceptible to tumor challenge. How- Acknowledgements-This work was supported by the Cancer Institute under Contract No. ever, by 14 weeks of treatment, shaved and unshaved National N01-CO-25423 with Litton Bionetics, Inc. mice were equally susceptible to tumor growth. This The technical assistance of Ms. Suzanne Lazar and Mr. suggested that either light entering through the eyes James Beard is acknowledged with thanks.

REFERENCE

Kripke, M. L., and M. S. Fisher (1976) J. Natl. Cancer Inst. 57, 211-215.

Target organ for a systemic effect of ultraviolet radiation.

Phorol-hernisrry and Pkorobiology, 1976, Vol. 24, pp. 599-600. Pergamon Press. Printed ill Great Britain RESEARCH NOTE TARGET ORGAN FOR A SYSTEMI...
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