Severe depletion of cellular thiols and glutathione-related enzymes of a carmustine-resistant L1210 strain associates with collateral sensitivity to cyclophosphamide.
Cancer Chemother Pharmacol
; 33(1): 85-8, 1993.
Article
em En
| MEDLINE
| ID: mdl-8269595
ABSTRACT
Cyclophosphamide (CPA) increased the life span of both carmustine (BCNU)-resistant (L1210/BCNU) and BCNU-sensitive L1210 (L1210/0) leukaemic mice; their sensitivity to CPA, however, was extremely different. The BCNU-resistant strain was much more sensitive (collaterally) to CPA than was its sensitive counterpart. The collateral sensitivity was accompanied by a severe reduction in the activity of glutathione-related enzymes and in protein thiol (SH) and non-protein SH levels in BCNU-resistant cells. The activity of glutathione reductase (GSSG-R) was 2 times higher in the L1210/0 cells than in the L1210/BCNU cells. Glutathione-S-transferase (GST) was also almost 2 times more active in the sensitive cells than in the resistant strain. To develop resistance against CPA with a single treatment (60 mg/kg) per passage, the L1210/BCNU strain needed 26 passages, whereas the L1210/0 strain required significantly fewer. The resistance developed against CPA was associated with a moderate elevation of thiols in the L1210/CPA cells, whereas this elevation was approximately 3 times more pronounced in the L1210/BCNU/CPA cells. The severely reduced activity of GST in the L1210/BCNU strain was markedly increased when these cells were made resistant to CPA; the GSSG-R activity, however, remained low, suggesting an irreversible injury of this enzyme by BCNU.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfidrila
/
Carmustina
/
Leucemia L1210
/
Ciclofosfamida
/
Glutationa Redutase
/
Glutationa Transferase
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
1993
Tipo de documento:
Article
País de afiliação:
Hungria