Effect of 7 beta-hydroxycholesterol on astrocyte primary cultures and derived spontaneously transformed cell lines: cytotoxicity and metabolism.
The lethal effect of 7 beta-hydroxycholesterol (7 beta-OHC) on neonatal rat astrocyte primary cultures and spontaneously transformed cell lines derived from them was investigated. Confluent astrocyte primary cultures were not affected by 30 microM 7 beta-OHC over a period of 72 h. In contrast, spontaneously transformed cells were killed by 20 microM 7 beta-OHC within the first 48 h. Further studies indicated that the cell lines metabolized 7 beta-OHC to a product the polarity of which was less than that of 7 beta-OHC. The metabolite was identified as 7 beta-OHC esterified on C-3 by naturally occurring fatty acids. Incubation of the cell lines with 0.5 microM metabolite markedly affected the cells within 24 h. These observations suggest that the 7 beta-OHC metabolite is implicated in the mechanism of action of 7 beta-OHC cytotoxicity on spontaneously transformed cells.
Kupferberg
A
A
Centre de Neurochimie du CNRS and INSERM U-44, Strasbourg, France.
Teller
G
G
Behr
P
P
Leray
C
C
Urban
P F
PF
Vincendon
G
G
Mersel
M
M
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002789:Cholesterol Oxidase / Q000378:metabolism; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D005227:Fatty Acids; D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; D002789:Cholesterol Oxidase