Interactions of 1-3 bis-(2-chloroethyl)-nitrosourea (NSC 409962) (BCNU) with clone DS19 of murine erythroleukemia cells (MELC).
Murine erythroleukemia cells (MELC) were incubated with BCNU in concentrations from 1 to 160 mu molar. The cytotoxicity was linear with concentration for 10 mu mol ar(GID15) to 40 mu molar (GID95). Incubation of MELC with BCNU induced striking morphological changes in the cell which include multinucleation and cell enlargement which appear to be linear with BCNU concentration in the range from 10 to 40 mu molar. Polykaryon formation was induced in 85% of MELC when exposed to 40 mu molar BCNU and was accompanied by marked increases in chromatin condensation and cellular fragility. The mean generation time for MELC(MGT) was increased from 14 h in control cultures to greater than 48 h in 40 mu molar BCNU. Hemoglobin synthesis in the presence of Me2SO was inhibited by 50% by exposure to 10 mu molar BCNU and to zero by exposure to 40 mu mo lar BCNU. These effects can be observed at 96 h after as little as 3 h of exposure to BCNU. The effects reported above are not reversible after washing cultures and reseeding them in fresh medium lacking BCNU. This is in contrast to cisplatin, another divalent alkylating agent in which the half-life of the crosslinks appears to be much shorter and in which washing and resuspension in fresh unsupplemented medium permits recovery of ability to replicate and to synthesize hemoglobin in the presence of Me2SO. The data supports the idea that the presence of single stranded breaks in DNA are required for induction of hemoglobin synthesis.
Gabelman
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D000818:Animals; D002330:Carmustine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects; D006454:Hemoglobins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology; D051379:Mice
D006454:Hemoglobins; D002330:Carmustine; D004121:Dimethyl Sulfoxide