EFFECT OF 2'-DEOXY-2'-(FLUOROMETHYLENE) CYTIDINE ON THE ULTRAVIOLET AND X-RAY-SENSITIVITY OF HELA-CELLS

The effects of treatment of HeLa cells with the antitumor nucleoside a nalog 2'-deoxy-2'-(fluoromethylene) cytidine (FMdC) on ultraviolet and X-ray sensitivity were examined. A 1-h pretreatment with FMdC increas ed cellular sensitivity to both X-rays and ultraviolet irradiation as determined by survival curve analysis. Increased sensitivity to killin g was accompanied by a clear reduction in the rate and extent of X-ray -induced DNA strand break repair and in the closure of excision repair -dependent DNA breaks following ultraviolet irradiation. These studies demonstrate that FMdC treatment compromises the repair of both ionizi ng (''short-patch'') and nonionizing (''long-patch'') DNA damage. The mechanism by which this is likely to occur is discussed. Based on thes e findings, it is likely that FMdC, in addition to possessing inherent antitumor activity, might provide additional antineoplastic benefit w hen administered in combination therapies with radiation.