Effect of psoralen plus ultraviolet A radiation on in vivo growth of melanoma cells.

Exposure of murine skin to UVB (280-320 nm) radiation accelerates the outgrowth of melanoma cells implanted into the irradiated site. Because many of the biological effects of psoralen plus UVA (320-400 nm) radiation (PUVA) resemble those of UVB radiation and because PUVA therapy is used extensively in the treatment of cutaneous diseases in humans, we determined the effect of PUVA on the growth of transplanted murine melanoma cells. Unshaved C3H/HeN(MTV-) mice were treated twice each week for 3 weeks with 0.4 mg 8-methoxypsoralen i.p. plus 4.25 kJ/m2 UVA radiation; syngeneic K1735 melanoma cells were then injected s.c. into the external ear. This treatment stimulated the outgrowth of the melanomas compared to that in untreated mice and mice treated with 8-methoxypsoralen or UVA alone. The use of a nonphototoxic, monofunctional psoralen plus UVA was equally effective, indicating that neither phototoxicity nor the ability to form DNA crosslinks was required for this effect. In vitro treatment of a murine keratinocyte cell line PAM 212 with PUVA caused the release of soluble factors that, when mixed with K1735 melanoma cells prior to injection, stimulated their outgrowth in vivo. These studies demonstrate that PUVA treatment can contribute to the pathogenesis of melanoma by exerting a stimulatory effect on the outgrowth of melanoma cells. Furthermore, they suggest that this effect may result from the ability of PUVA to cause the release of stimulatory factors from keratinocytes.