A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells.
The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.
D000666:Amphotericin B / Q000633:toxicity; D002330:Carmustine / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008130:Lomustine / Q000633:toxicity; D008223:Lymphoma; D009374:Neoplasms, Experimental; D009607:Nitrosourea Compounds / Q000633:toxicity*; D012673:Semustine / Q000633:toxicity; D013997:Time Factors; D014801:Vitamin A / Q000627:therapeutic use
D009607:Nitrosourea Compounds; D014801:Vitamin A; D012673:Semustine; D008130:Lomustine; D000666:Amphotericin B; D002330:Carmustine