Effects of topoisomerase I-targeted drugs on radiation response of L5178Y sublines differentially radiation and drug sensitive.
The murine L5178Y (LY) lymphoma sublines, LY-R (radiation resistant) and LY-S (radiation sensitive) display a difference in susceptibility to camptothecin (CPT): LY-S cells are less sensitive to killing by this inhibitor of topoisomerase I than LY-R cells. Post-treatment (CPT present until 3 h after irradiation) sensitizes only LY-S cells. In agreement with this, only in LY-S cells is the relative number of DNA-protein cross-links formed after treatment with CPT + X higher than expected for additivity of X-ray and CPT-induced damage. The pattern of changes in the labelling indices and cell cycle distribution in cells that underwent combined treatment is essentially like that seen for single-agent treatment: for LY-S cells like that for radiation, for LY-R cells like that for CPT. We found no direct relation between the patterns of cell cycle distributions and the enhancement of the lethal effect of X-irradiation by CPT post-treatment. The sublines are not markedly differentially sensitive to beta-lapachone, which modifies topoisomerase I activity, and not sensitized to X-rays by post-irradiation treatment with the drug.
Szumiel
I
I
Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
Buraczewska
I
I
Gradzka
I
I
Gasinska
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D007940:Leukemia L5178 / Q000188:drug therapy* / Q000201:enzymology / Q000532:radiotherapy*; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D009285:Naphthoquinones; D011838:Radiation-Sensitizing Agents; D059004:Topoisomerase I Inhibitors; C014638:beta-lapachone; D002166:Camptothecin