Glutathione and cellular response of ACNU-resistant rat glioma sublines to drugs and radiation.
Three ACNU-resistant sublines (R1, R3 and R12) from rat glioma 9L cells showed cross-resistance to vinblastine, adriamycin, and VP-16. Among these, the R3 subline also acquired radioresistance under aerobic conditions. Total glutathione levels in these sublines were elevated 2- to 3-fold. Treatment of the cells with BSO, a specific inhibitor of GSH synthesis, resulted in decreased intracellular total glutathione levels in all 4 cell lines to about 10% of control levels. However, sensitivity to radiation or to chemicals did not change accordingly. Treatment of 9L cells with OTZ, a precursor of cysteine, resulted in a rise in intracellular GSH levels but it did not correlate with sensitivity to X-ray or to ACNU. These results suggest that, in terms of cellular sensitivity to radiation or ACNU, total glutathione level alone cannot serve as a predictive indicator.
Saito
Y
Y
Department of Neurosurgery, Hiroshima University School of Medicine, Japan.
Nakada
Y
Y
Hotta
T
T
Mikami
T
T
Kurisu
K
K
Yamada
K
K
Kiya
K
K
Kawamoto
K
K
Uozumi
T
T
D000818:Animals; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology*; D005910:Glioma; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D015376:Nimustine / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014747:Vinblastine / Q000494:pharmacology*
D013844:Thiazoles; D053778:Thiazolidines; D015376:Nimustine; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid