The influence of radiation and chemotherapy-related DNA strand breaks on carcinogenesis: An evaluation

Purpose: DNA strand breaks are believed to induce carcinogenesis. This stud y was conducted to analyze induction and repair of irradiation- and chemoth erapy-related strand breaks in vitro. Methods: Friend Leukemia cells were exposed to irradiation and various chem otherapeutic agents at different doses and concentrations. Occurence of str and breaks was determined fluorometrically, measuring the rate of DNA unwin ding immediatly after exposure and 24 hours later. Results: The amount of double-stranded DNA decreased significantly for irra diation, doxorubicin, dactinomycin and etoposide (p less than or equal to 0 .05, t-test). After 24 hours free of exposure, the persistent damage was de tectable for all of these agents but not for irradiated cells, with DNA str and breaks being decreased for etoposide, unchanged for doxorubicin and inc reased for methotrexate as well as for dactinomycin. Conclusions: Severe DNA damage is induced by various chemotherapeutic agent s and by irradiation. While repair of chemotherapy-related strand breaks ma y remain incomplete or prolonged for some chemotherapeutic agents, repair o f radiation induced strand breaks is faster and more complete. Therefore ch emotherapy-related carcinogenesis may partially be explained by prolonged p ersistence of DNA strand breaks.