Kinetics of Excision Repair Synthesis Induced by N -Acetoxy-2-acetylaminofluorene and Ultraviolet Irradiation in Human Diploid Fibroblasts

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Abstract
The rate of DNA repair synthesis was studied with the use of [3H)thymidine to pulse confluent, hydroxyurea-treated human diploid fibroblasts (WI-38) at intervals up to 76 hours after treatment with either 45 erg UV irradiation/mm2 or 10 μM N-ace-toxy-2-acetylaminofluorene (NA-AAF). These doses induced equal repair incorporation during the first 4 hours after exposure. During this Initial period, the UV-treated cells showed an almost linear increase in repair synthesis, whereas the chemically treated cells showed a lag from 0 to 30 minutes, followed by a linear incorporation from 30 minutes to 4 hours. After UV exposure, the rate of DNA repair synthesis was highest from 0 to 4 hours and decreased considerably by 8–12 hours, so that by 24–28 hours, the rate was only 20% of that from 0 to 4 hours; by 72–76 hours, incorporation was close to levels of the nonirradiated controls. The rate of repair synthesis after continuous NA-AAF administration decreased much more slowly, and by 72–76 hours was still about 50% of that from 0 to 4 hours. Removal of NA-AAF from the cultures at 4 hours reduced the 72- to 76- hour Incorporation to 30% of the 0- to 4-hour value. These characteristic profiles of DNA repair synthesis were observed through a range of doses of both UV and NA-AAF, from conditions where cell survival was good to conditions approaching lethality.

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