Apoptogenic effect of the lipophilic o-naphthoquinone CG 10-248 on rat hepatocytes: light and electron microscopy studies.
CG 10-248 (3,4-dihydro-2,2-dimethyl-9-chloro-2H-naphtho[1,2b]pyran-5,6-dione; CG-NQ), a beta-lapachone analogue, modified the ultrastructure of rat hepatocytes, as demonstrated by light and electron microscopy. After 4 h incubation with 100 microM CG-NQ, the following effects were observed: (a) nuclear chromatin condensation; (b) chromatin fragmentation; (c) displacement of mitochondria, concentrated around the nucleus; (d) disruption or expansion of mitochondrial outer or inner membranes, respectively; (e) displacement and alteration of endoplasmic reticulum (rough and smooth); (f) decrease of microvilli; (g) blebbing of plasma membrane and production of apoptotic bodies formed by folding of plasma membrane fragments around mitochondria or peroxysomes; and (h) production of hydrogen peroxide. Expression of such effects varied according to hepatocyte samples and taken together strongly support an apoptotic action of CG-NQ dependent on "reactive oxygen species".
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D022081:Cell Surface Extensions / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006861:Hydrogen Peroxide / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008871:Microvilli / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009285:Naphthoquinones / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
C480829:3,4-dihydro-2,2-dimethyl-9-chloro-2H-naphtho(1,2b)pyran-5,6-dione; D002843:Chromatin; D009285:Naphthoquinones; D006861:Hydrogen Peroxide