INHIBITION OF NEUTROPHIL ELASTASE SUPPRESSES THE DEVELOPMENT OF SKIN TUMORS IN HAIRLESS MICE

In this study we investigated whether a reduction in neutrophil elasta se activity in mice would alter the development of ultraviolet B or ch emically induced skin tumors. A mutant strain of neutrophil elastase-d eficient mice was developed by crossing beige mice with SKH 1 hairless mice. Ultraviolet irradiation three times per week for 20 wk develope d an average of 10 tumors per normal mouse, whereas elastase-deficient hairless mice receiving the same treatment developed only 0.4 tumors per mouse. Benzopyrene administered topically for 20 wk resulted in an average of seven tumors per control mouse, while similar treatment to elastase-deficient hairless mice reduced the tumor count to 0.2 per m ouse. Two small molecular weight elastase inhibitors, which were shown to inhibit mouse neutrophil elastase, were administered subcutaneousl y to normal SKH-1 mice during 16 wk of ultraviolet B exposure. Both in hibitors significantly reduced the incidence of ultraviolet B-induced tumors. When control and elastase-deficient mice were immunized with 2 ,4,6-trinitrochlorobenzene and oxazolone, both molecules elicited a si gnificant contact hypersensitivity response. Ultraviolet B irradiation prior to immunization at a nonirradiated site completely suppressed t he induction of contact hypersensitivity in both the normal and the de ficient mice, suggesting that prevention of systemic immunosuppression was not the reason for the resistance to skin tumors observed in the elastase-deficient mice. The results suggest that neutrophil elastase can be an important factor in squamous cell tumor development.