Hyperthermia blocks reversibility of hydroxyurea and bipyridine induced synergistic inhibition of DNA biosynthesis in P388 murine leukemia cells.
The influence of hyperthermia (42 degrees C) on the reversibility of hydroxyurea- and the iron-chelator 2,2'-bipyridine-induced synergistic inhibition of DNA biosynthesis was studied in intact P388 murine lymphocytic leukemia cells in vitro. The cytotoxicity caused by hydroxyurea alone and in combination with bipyridine for 3 h at 37 degrees C and 42 degrees C was found to be completely reversible. However, the inhibition of DNA biosynthesis was irreversible when hydroxyurea- and iron-chelate-treated and washed cells at 37 degrees C were subjected to hyperthermia at 42 degrees C. A potentiation in DNA biosynthesis was also observed when the P388 cells were subjected to hyperthermia along with the combination of hydroxyurea and 2,2'-bipyridine. These effects are probably due to the heat-sensitive nature of the ribonucleotide reductase enzyme, the target site of the effect of hydroxyurea and 2,2'-bipyridine.
Satyamoorthy
K
K
Cancer Research Institute, Tata Memorial Center, Parel, Bombay, India.
Chitnis
M P
MP
D015082:2,2'-Dipyridyl / Q000494:pharmacology*; D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D006358:Hot Temperature; D006918:Hydroxyurea / Q000494:pharmacology*; D007700:Kinetics; D007941:Leukemia P388 / Q000378:metabolism* / Q000473:pathology; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D011725:Pyridines / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D011725:Pyridines; D015082:2,2'-Dipyridyl; D013936:Thymidine; D006918:Hydroxyurea