Cross-resistance pattern in brain tumour cells resistant to antitumour chloroethylnitrosoureas.
We tested acquired resistance and cross-resistance of brain tumour cells after repeated treatments of antitumour agents including chloroethylnitrosoureas (CENUs) in clinical use for brain tumour chemotherapy. Within ten repeated 2-day incubation periods with either 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) or methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyr anoside (MCNU), brain tumour cells (9L) developed high degrees of resistance to these drugs, as evidenced by about 3- and 6-fold increases, respectively, at the 10% survival dose (SD10). The resistance has unchanged with time after termination of challenging treatments. Repeated challenges with bleomycin (BLM), cis-diaminedichloroplatinum (II) (CDDP), and methotrexate (MTX) did not develop a significant resistance. ACNU-resistant (9L/ACNU) cells showed complete cross-resistance to MCNU, and MCNU-resistant (9L/MCNU) cells to ACNU. Drug sensitivity to other DNA-damaging agents (BLM, NCS, CDDP, etoposide) than CENUs fluctuated to a lesser extent among 9L parent, 9L/ACNU, and 9L/MCNU cells. These data suggest clinical disadvantage of prolonged adjuvant CENU chemotherapy and advantage of combined CENU chemotherapy with other agents than CENUs in brain tumours.
Neurosurgical Service, Akita University Hospital, Japan.
K
K
Mineura
Y
Y
Ishiyama
M
M
Kowada
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy*; D004351:Drug Resistance / Q000502:physiology; D015376:Nimustine / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D015376:Nimustine; C020766:ranimustine