[Disruption of DNA synthesis and structure of mouse L1210 leukemia cells, sensitive and resistant to 1-methyl-1 nitrosourea and 1,3-bis(2-chloroethyl)-1-nitrosourea in vivo].
Leukemia L1210 cells with acquired resistance to 1-methyl-1-nitrosourea (MNU) (L1210/MNU) and 1.3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (L1210/BCNU) were developed from leukemia L1210 cells sensitive to these drugs (L1210/0). The modal chromosome number of leukemia L1210/MNU and L1210/BCNU cells increases from 40 (L1210/0) to 41. It was shown that in leukemia L1210/MNU cells the inhibition of DNA synthesis after MNU administration in a therapeutic dose (80 mg/kg) is lasted within 24 hours, while that in leukemia L1210/0 cell--within 96 hours. After administration of BCNU (20 mg/kg) inhibition of DNA synthesis in leukemia L1210/BCNU cells reached of 50% of control in comparison with practically complete inhibition of DNA synthesis in leukemia L1210/0 cells. Centrifugation on alkaline sucrose density gradients revealed no differences in the rate of sedimentation of leukemia L1210/0, L1210/MNU and L1210/BCNU cell lysates. After 1 hour treatment with MNU of mice bearing L1210/MNU and L1210/0 leukemia cells single-strand breaks in DNA were determined. After 4 hours these strand-breaks retained in leukemia L1210/0 cells, but were eliminated in leukemia L1210/MNU cells. Administration of BCNU to mice with leukemia L1210/0 and L1210/BCNU cells resulted in both cases in the production of DNA aggregates. There is no complete cross-resistance between MNU and BCNU which allows a substitution of these drugs providing for the increase in their therapeutic efficiency.
D000818:Animals; D002330:Carmustine / Q000494:pharmacology*; D002499:Centrifugation, Density Gradient; D002869:Chromosome Aberrations / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004277:DNA, Single-Stranded / Q000032:analysis; D004351:Drug Resistance; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism*; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008970:Molecular Weight; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D009690:Nucleic Acid Conformation / Q000187:drug effects
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D009607:Nitrosourea Compounds; D008770:Methylnitrosourea; D002330:Carmustine
Narusheniia v sinteze i strukture DNK kletok leĭkoza L1210 mysheĭ, chuvstvitel'nykh i rezistentnykh k 1-metil-1-nitrozomochevine i 1,3-bis(2-khlorétil)-1-nitrozomochevine in vivo.