TREATMENT WITH TOPICAL KHELLIN IN COMBINATION WITH ULTRAVIOLET-A OR SOLAR-SIMULATED RADIATION IS CARCINOGENIC TO LIGHTLY PIGMENTED HAIRLESSMICE

Khellin is used together with either UVA irradiation or sun exposure i n the treatment of vitiligo. The purpose of this study was to investig ate the carcinogenic effect of topically applied khellin together with UVA or solar simulated radiation (SSR) in lightly pigmented C3H/Tif m ice. For comparison purposes a 0.1% 8-methoxypsoralen (8-MOP) cream wa s also tested in combination with SSR. Fifty mu l of a 5% khellin crea m, a 0.1% 8-MOP cream, or a cream without active substances were sprea d uniformly on the back of the mice 30 minutes before UVA or SSR irrad iation. All mice were irradiated 3 times a week until age or skin tumo r development necessitated killing. Treatment with topical khellin and UVA irradiation was carcinogenic to lightly pigmented hairless mice, time to 50% of the mice had developed one tumor (t(50)) was 507 days. This indicates that the combination of topical khellin and UVA radiati on, formerly expected to be rather innocuous, is carcinogenic to mice. Also the combination of khellin and SSR (t(50) = 268 days) enhanced s kin tumor development significantly compared with control cream and SS R (t(50) = 330 days), P<0.05. In addition, the combination of khellin and SSR was found to have the same carcinogenic effect as treatment wi th 0.1% 8-MOP and SSR (t(50) = 262 days). This study shows that topica lly applied khellin increases the carcinogenic effect of both UVA and sunlight.