Differential proto-oncogene mRNA induction from rats treated with peroxisome proliferators.
After experimental treatment of rats with clofibrate or ciprofibrate, two peroxisomes proliferators with hypolipidemic activity, RNAs were prepared from liver, kidney, heart and brain; hybridization was done with DNA probes for c-myc and c-Ha-ras oncogenes and for cyanide insensitive Acyl CoA oxidase, a peroxisomal protein. c-myc mRNA is highly abundant in liver and at a lower extent in kidney, especially after treatment with ciprofibrate; clofibrate also allows a c-myc mRNA increase, but at a lower extent. c-Ha-ras, which is already expressed in all tested tissues from control animals, is stimulated by clofibrate and ciprofibrate treatments. Comparatively these compounds stimulate the cyanide insensitive Acyl CoA oxidase expression as well as they increase the somatic index of liver and kidney. From these experiments we suggest that hepatocarcinogenesis triggered by some hypolipidemic agents could be mediated by proto-oncogene mRNA level increase.
Cherkaoui Malki
M
M
Laboratoire de Biochimie et Biologie Moléculaire (URA CNRS 531), Université de Franche Comté, Besançon, France.
Lone
Y C
YC
Corral-Debrinski
M
M
Latruffe
N
N
D042962:Acyl-CoA Oxidase; D000818:Animals; D002994:Clofibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D058607:Fibric Acids; D005786:Gene Expression Regulation; D016259:Genes, myc; D011905:Genes, ras; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D009928:Organ Specificity; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D002995:Clofibric Acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; C019304:ciprofibrate; D002994:Clofibrate