[Development of ACNU-resistant meningeal gliomatosis models: establishment of resistant rat glioma subline against ACNU].

Induction in vivo of resistance of C6 rat glioma and 9L rat glioma to ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride] was studied and ACNU-resistant rat meningeal gliomatosis models were developed by using these resistant glioma sublines. Rapid acquisition of resistance to the agent was present at 2nd transplant generation in both glioma lines. Cellular resistance to ACNU remained unchanged in the absence of drug over 5 transplant generations in vivo in spite of the fact that the drug treatment was discontinued at the 5th generation after a complete resistance was induced. On the other hand, the degree of resistance of 9L resistant subline established by only once ACNU treatment was found to be decreased after 5 transplant generations in vitro. Degree of resistance at the cellular level was observed with each subline by in vitro technique and compared with each other. Each subline was found to have different degree of resistance: 9L resistant subline showed higher resistance than C6 resistant subline, and the differences in degree of resistance between 9L resistant subline and C6 resistant subline were approximately 750 and 20, respectively, when they were expressed as ratios of IC50 (drug concentration for 50% growth inhibition) for the resistant subline to the original one.