The influence of radiation and chemotherapy-related DNA strand breaks on carcinogenesis: an evaluation.
OBJECTIVE
DNA strand breaks are believed to induce carcinogenesis. This study was conducted to analyze induction and repair of irradiation- and chemotherapy-related strand breaks in vitro.


METHODS
Friend Leukemia cells were exposed to irradiation and various chemotherapeutic agents at different doses and concentrations. Occurrence of strand breaks was determined fluorometrically, measuring the rate of DNA unwinding immediately after exposure and 24 hours later.


RESULTS
The amount of double-stranded DNA decreased significantly for irradiation, doxorubicin, dactinomycin and etoposide (p < or = 0.05, t-test). After 24 hours free of exposure, the persistent damage was detectable for all of these agents but not for irradiated cells, with DNA strand breaks being decreased for etoposide, unchanged for doxorubicin and increased for methotrexate as well as for dactinomycin.


CONCLUSIONS
Severe DNA damage is induced by various chemotherapeutic agents and by irradiation. While repair of chemotherapy-related strand breaks may remain incomplete or prolonged for some chemotherapeutic agents, repair of radiation induced strand breaks is faster and more complete. Therefore chemotherapy-related carcinogenesis may partially be explained by prolonged persistence of DNA strand breaks.
Froelich
J J
JJ
Medizinisches Zentrum für Radiologie, Abteilung für Strahlendiagnostik, Klinikum der Philipps-Universität, Marburg, Germany. froehlic@mailer.uni-marburg.de
Schneller
F R
FR
Zahn
R K
RK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000528:radiation effects*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate