Catechol cytotoxicity in vitro: induction of glioblastoma cell death by apoptosis.
The exposure to benzene is a public health problem. Although the most well-known effect of benzene is hematopoietic toxicity, there is little information about the benzene and its metabolites effects on the central nervous system (CNS). This study examined the toxic effects of 1,2-dihydroxybenzene (catechol), a benzene metabolite, to human glioblastoma GL-15 cells. GL-15 cell cultures were used as a model to provide more information about the toxic effects of aromatic compounds to the CNS. Catechol induced time- and concentration-dependent cytotoxic effects. Morphological changes, such as the retraction of the cytoplasm and chromatin clumping, were seen in cells exposed to 200 microM catechol for 48 hours. In cells exposed to 600 microM catechol for 48 hours, 78.0% of them presented condensed nuclei, and the Comet assay showed DNA damage. The percentage of cells labeled with annexin V (apoptotic cells) was greater in the group exposed to catechol (20.7%) than in control cells (0.4%). Exposure to catechol at concentrations greater than 100 microM enhanced Bax levels, and a decrease in Bcl-2 level was observed after the exposure to 600 microM catechol for 48 hours. Furthermore, catechol depleted reduced glutathione. Hence, catechol induced cell death mainly by apoptosis.
de Oliveira
D M
DM
Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Bahia, Brazil.
Pitanga
B P S
BP
Grangeiro
M S
MS
Lima
R M F
RM
Costa
M F D
MF
Costa
S L
SL
Clarêncio
J
J
El-Bachá
R S
RS
D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002396:Catechols / Q000633:toxicity*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D002396:Catechols; D004785:Environmental Pollutants; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D005978:Glutathione; C034221:catechol