Sensitivity of testis tumour cells to chemotherapeutic drugs: role of detoxifying pathways.
In contrast to most other types of cancer, metastatic testicular germ cell tumours (TGCT) are cured in most patients using cisplatin-based combination chemotherapy. The biochemical mechanisms underlying this sensitivity have not been defined. Drug detoxification can modulate response to chemotherapy in vivo and in vitro, and therefore we measured levels of glutathione (GSH), glutathione-S-transferase (GST) and both constitutive and cisplatin- and dexamethasone-induced levels of metallothionein (MT) in five human testis tumour cell lines. The levels were compared with those in five human bladder cancer cell lines and two cell lines with cisplatin resistance acquired in vitro. GSH levels were relatively low in the testis tumour cell lines, as might be expected in drug-sensitive cells, and there was a 77-fold increase in GSH levels in the cisplatin-resistant testis tumour cell line. GST levels were similar in the two cell types, while metallothionein levels were relatively high in the testis tumour cell lines. These data indicate that GSH may contribute to the sensitivity of TGCT to chemotherapy, and that GSH expression may be involved in the acquisition of cisplatin resistance in these tumours.
Masters
J R
JR
Institute of Urology and Nephrology, University College of London, U.K.
Thomas
R
R
Hall
A G
AG
Hogarth
L
L
Matheson
E C
EC
Cattan
A R
AR
Lohrer
H
H
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D015153:Blotting, Western; D002945:Cisplatin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D018237:Germinoma / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D003907:Dexamethasone; D008668:Metallothionein; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin