Effect of oxysterol derivatives on the time course development of hepatocarcinoma in transgenic mice.
Among their biological properties, several oxysterols display a stronger toxicity towards tumor cells than towards normal cells. Water-soluble phosphodiesters of 7 beta-hydroxycholesterol (JB69 and XA29), that were proved to retain a specific antitumoral activity in vitro, have been recently developed, allowing in vivo studies. They have been assayed on transgenic mice expressing the Large T antigen of SV40 in their liver and developing systematically hepatocarcinoma within 8 months. We show that JB69 and XA29 administered intraperitoneally into transgenic mice, before the onset of adenoma, may prevent or delay the tumor development. Consequently, oxysterol derivatives might constitute new efficient prodrugs against naturally occurring tumors.
Allemand
I
I
Laboratoire de Génétique et Pathologie Expérimentale, INSERM CJF 90-03, ICGM, Paris, France.
Christ
M
M
Pannecoucke
X
X
Molina
T
T
Luu
B
B
Briand
P
P
D000236:Adenoma / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003856:Deoxyuracil Nucleotides / Q000627:therapeutic use*; D006888:Hydroxycholesterols / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008940:Mitotic Index; D009954:Ornithine Carbamoyltransferase / Q000097:blood; D013539:Simian virus 40 / Q000235:genetics; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D003856:Deoxyuracil Nucleotides; D006888:Hydroxycholesterols; C068425:JB 69; C068427:3-(7 beta-hydroxycholesteryl) 5'-thymidylyl monophosphate; D013938:Thymidine Monophosphate; D009954:Ornithine Carbamoyltransferase