Differential potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea by α-difluoromethylornithine in chloroethylnitrosourea-sensitive and -resistant 91 rat brain tumor cells in vitro

α-Difluoromethylomithine, an enzyme-activated, irreversible inhibitor of omithine decarboxylase, inhibited the growth of both chloroethyl nitrosourea-sensitive and -esistant 9L rat brain tumor cells in vitro. After 48 hr of treatment with 10 mM α-difluoromethylomithine, the putrescine and spermidine contents of both resistant and sensitive cells were less than 5% of control levels, but the spermine levelwas slightly elevated. The cytotoxicity of 1,3-bis(2-chloroethyl)-1 -nitrosourea, as measured by a colony-forming efficiency assay, was significantly increased in α-difluoromethylomithine-pretreated sensitive cells but not in resistant cells treated with this polyamine inhibitor. With the sister chromatid exchange assay, we found thatα-difluoromethylornithine pretreatment increased 1,3-bis(2-chloroethyl)-1 -nitrosourea-induced damage to chromosomes in sensitive but not in resistant cells.