Differential potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine in chloroethylnitrosourea-sensitive and -resistant 9L rat brain tumor cells in vitro.
alpha-Difluoromethylornithine, an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, inhibited the growth of both chloroethylnitrosourea-sensitive and -resistant 9L rat brain tumor cells in vitro. After 48 hr of treatment with 10 mM alpha-difluoromethylornithine, the putrescine and spermidine contents of both resistant and sensitive cells were less than 5% of control levels, but the spermine level was slightly elevated. The cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea, as measured by a colony-forming efficiency assay, was significantly increased in alpha-difluoromethylornithine-pretreated sensitive cells but not in resistant cells treated with this polyamine inhibitor. With the sister chromatid exchange assay, we found that alpha-difluoromethylornithine pretreatment increased 1,3-bis(2-chloroethyl)-1-nitrosourea-induced damage to chromosomes in sensitive but not in resistant cells.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D002330:Carmustine / Q000494:pharmacology*; D002460:Cell Line; D004351:Drug Resistance; D004357:Drug Synergism; D000518:Eflornithine; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000970:Antineoplastic Agents; D011073:Polyamines; D009952:Ornithine; D002330:Carmustine; D000518:Eflornithine