Mitochondrial damage following exposure of organotypic cultures of human malignant gliomas to 2-chloro- and 2-bromo-2'-deoxyadenosine.
The effects of 2-chloro-2'-deoxyadenosine (cladribine, 2-CdA) and a closely related compound 2-bromo-2'-deoxyadenosine (2-BdA) on organotypic cultures of human malignant gliomas were studied with the use of electron microscopy. The cultures grown from surgical biopsies included six glioblastomas, three anaplastic astrocytomas and low-grade fibrillary astrocytoma. After 6 to 10 days of the in vitro growth the cultures were exposed to 0.3-10 microM 2-CdA or 2-BdA for 1 to 10 days. Mitochondrial swelling and disappearance of cristae following exposure to the tested substances were observed, but only in highly anaplastic (low-differentiated) tumor cells. The mitochondrial toxicity was dose- and time-dependent, and no difference was found between the effect of 2-CdA and 2-BdA.
Matyja
E
E
Department of Neuropathology, Medical Research Centre, Polish Academy of Sciences, Warszawa.
Grieb
P
P
Ryba
M
M
Jagielski
J
J
Mossakowski
M J
MJ
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001254:Astrocytoma / Q000473:pathology / Q000648:ultrastructure*; D002465:Cell Movement; D017338:Cladribine / Q000009:adverse effects* / Q000494:pharmacology*; D046508:Culture Techniques; D005909:Glioblastoma / Q000473:pathology / Q000648:ultrastructure*; D005910:Glioma / Q000473:pathology / Q000648:ultrastructure*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology*
D000970:Antineoplastic Agents; D017338:Cladribine