Comparison of effects of iron and calcium chelators on the response of L5178Y sublines to X-rays and H2O2.
The L5178Y murine lymphoma subline LY-R is twofold more resistant to killing by ionizing radiation than the subline LY-S. In contrast, LY-R cells are more sensitive to killing by hydrogen peroxide: at 37 degrees C LY-R cells are 1.4 times more sensitive to the killing effect of H2O2 than LY-S cells. Pretreatment with the iron chelator desferroxamine followed by hydrogen peroxide treatment at 37 degrees C gives a considerable sparing effect, which is substantially greater for the LY-R subline than for the LY-S subline. This is reflected in the initial DNA damage (estimated by single cell gel electrophoresis), survival and mutation frequency in the HGPRT locus. Similar results have been obtained with calcium chelators, which, according to recent findings (Sandström and Granström 1993), also are efficient iron chelators. In contrast, the response to X-rays is not modified by the above chelators, with the exception of mutation frequencies: lower mutant numbers are found in desferroxamine pretreated LY-R cells.
Kruszewski
M
M
Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
Green
M H
MH
Lowe
J E
JE
Szumiel
I
I
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004587:Electrophoresis, Agar Gel / Q000379:methods; D016257:Fura-2 / Q000031:analogs & derivatives / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007940:Leukemia L5178; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D011836:Radiation Tolerance / Q000187:drug effects; D012044:Regression Analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays
D000634:Aminoquinolines; D016587:Antimutagenic Agents; D002614:Chelating Agents; D009153:Mutagens; C049925:fura-2-am; D006861:Hydrogen Peroxide; D007041:Hypoxanthine Phosphoribosyltransferase; D003676:Deferoxamine; C035739:Quin2; D002118:Calcium; D016257:Fura-2