Psoralen plus ultraviolet radiation-induced inhibition of DNA synthesis and viability in human lymphoid cells in vitro.

Abstract

Abstract— 8‐Methoxypsoralen (8‐MOP) plus high intensity long wavelength ultraviolet radiation (UV‐A) is presently being used to induce remissions of psoriasis and mycosis fungoides. Previous studies demonstrated inhibition of DNA synthesis in circulating leukocytes from some patients during this therapy. The present study is designed to determine whether conditions of 8‐MOP concentration and UV‐A exposure attained during therapy might be sufficient to result directly in decreased lymphoid cell DNA synthesis and viability in vitro. Tritiated thymidine (3HTdR) incorporation and cell growth in suspension culture following UV‐A exposure alone or with therapeutic concentrations of 8‐MOP was examined in peripheral blood lymphocytes and in Ebstein‐Barr virus transformed human lymphoblas‐toid cell lines. UV‐A exposure alone induced a dose‐dependent inhibition of HTdR incorporation in both types of lymphoid cells (3000 J/m2 resulted in 77% of control 3HTdR incorporation). Pre‐incubation with 0.1 μg/m/ 8‐MOP before UV‐A exposure induced a significantly greater inhibition of 3HTdR incorporation (3000 J/m2 resulted in 61% of control 3HTdR incorporation). Greater inhibition of 3HTdR incorporation was observed by preincubation of the lymphoblastoid cells with 1.0μg/mC 8‐MOP (3000 J/m2 resulted in 41% of control) but not in the lymphocytes (3000 J/m2 resulted in 63% of control). The concentration of viable lymphoblastoid cells did not decrease below the original concentration after the highest dose of UV‐A alone (29,000 J/m2) but preincubation with 0.1 μg/mC 8‐MOP resulted in 40% survival after 3000 J/m2 (D37 approximately 3000 J/m2) and preincubation with 1.0 μg/ 8‐MOP resulted in 0.6% survival after 3000 J/,2 (D37 approximately 800 J/m2). This study suggests that the low doses of 8‐MOP and UV‐A received by patients' lymphocytes may be sufficient to explain the decreased DNA synthesis found in their circulating leucocytes. The long term consequences of such damage remain to be determined.