[The role of N-nitrosourea-induced changes in the nucleoid structure and activity of repair enzymes in the development of drug resistance in mice with leukemia L1210].
Using centrifugation of the nucleoid in a neutral sucrose gradient, the damages in the secondary structure of DNA and the activity of repair enzymes, such as DNA-polymerases alpha and beta and poly(ADP-riboso) polymerase, induced by 1-methyl-nitrosourea (MNU) and 1.3-bis (2-chloroethyl)-1-nitrosourea (BCNU) injected at maximal nonlethal single doses to mice bearing parent leukemia cells (L1210/0) and resistant to MNU and BCNU leukemia L1210 cells (L1210/MNU and L1210/BCNU), were studied. The MNU-induced production of single-strand breaks in L1210/0 and L1210/MNU cells was more conspicuous in newly replicated DNA than in those in preexisting DNA. A more fast repair of the damages in newly replicated DNA was detected in L1210/BCNU and especially in L1210/MNU leukemia cells as compared with L1210/0 cells. The data obtained suggest that there are prone errors in the repair of DNA template, since most of the single-strand breaks were revealed in the newly replicated DNA synthesized on the repaired DNA. The repair of DNA damages in L1210/BCNU and especially in L1210/MNU cells was accompanied by the activation of DNA-polymerases alpha and beta and poly(ADP-riboso)polymerase. Both DNA-polymerases--alpha and beta--were shown to be involved in repair of DNA damages induced by MNU and only DNA-polymerase beta was involved in the repair of damages induced by BCNU.
Durdyeva
E D
ED
Ponomarenko
N A
NA
Kukushkina
G V
GV
Gorbacheva
L B
LB
D000818:Animals; D002330:Carmustine / Q000494:pharmacology*; D002467:Cell Nucleus / Q000201:enzymology; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D007939:Leukemia L1210 / Q000235:genetics / Q000378:metabolism*; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D008770:Methylnitrosourea; D004259:DNA-Directed DNA Polymerase; D002330:Carmustine
Rol' indutsirovannykh N-nitrozomochevinami izmeneniĭ v strukture nukleoida i aktivnosti fermenta reparatsii v proiavlenii lekarstvennoĭ ustoĭchivosti u mysheĭ s leĭkozom L1210.