title: Mitochondrial damage following exposure of organotypic cultures of human malignant gliomas to 2-chloro- and 2-bromo-2'-deoxyadenosine.
abstract: 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.
authors.affiliation: Department of Neuropathology, Medical Research Centre, Polish Academy of Sciences, Warszawa.
authors.forename: E
authors.initials: E
authors.lastname: Matyja
authors.forename: P
authors.initials: P
authors.lastname: Grieb
authors.forename: M
authors.initials: M
authors.lastname: Ryba
authors.forename: J
authors.initials: J
authors.lastname: Jagielski
authors.forename: M J
authors.initials: MJ
authors.lastname: Mossakowski
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine