Red blood cell glutathione levels in lung cancer patients treated by radiation and continuously infused carboplatin.
Intrinsic resistance in non-small cell lung cancer (NSCLC) curtails the efficacy of chemotherapy and radiotherapy. Glutathione (GSH) may be one of the factors responsible for this phenomenon as it counteracts the cytotoxic effects of platinum containing drugs and radiation. GSH levels were studied in red blood cells of seven smoking patients with NSCLC treated with continuously infused carboplatin and concomitant radiotherapy for 6 weeks. The levels of red blood cell GSH remained unchanged during prolonged combined treatment and were similar to those in non-smoking volunteers. In vitro, in a cell-free system, it was demonstrated that GSH-platinum complex formation occurred with both cisplatin and carboplatin in a time-dependent manner and that this formation decreased total GSH as measured with Tietze's method. This implies that increased consumption of GSH by platinum and free radicals produced by carboplatin and radiation, respectively, seems to induce GSH in red blood cells resulting in an unchanged total GSH level. Although GSH in red blood cells may be relevant as a detoxification pool for platinum, it had no impact on response rates in these patients with NSCLC.
Groen
H J
HJ
Department of Pulmonary Diseases, University Hospital, Groningen, The Netherlands.
Meijer
C
C
De Vries
E G
EG
Mulder
N H
NH
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002474:Cell-Free System; D003131:Combined Modality Therapy; D004912:Erythrocytes / Q000737:chemistry*; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D010984:Platinum / Q000378:metabolism; D012907:Smoking / Q000097:blood
D000970:Antineoplastic Agents; D010984:Platinum; D016190:Carboplatin; D005978:Glutathione