Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo.
Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl-nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5-fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells.
Yoshida
T K
TK
Department of Neurosurgery, Osaka University Medical School, Japan.
Shimizu
K
K
Koulousakis
A
A
Sturm
V
V
Beuls
E
E
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance; D008297:Male; D009368:Neoplasm Transplantation; D015376:Nimustine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D015376:Nimustine