COMPARISON OF CONSTITUTIVE AND INDUCIBLE LEVELS OF EXPRESSION OF PEROXISOMAL BETA-OXIDATION AND CATALASE GENES IN LIVER AND EXTRAHEPATIC TISSUES OF RAT

  • 15 September 1988
    • journal article
    • research article
    • Vol. 48  (18) , 5316-5324
Abstract
Previous studies from our laboratories have shown that carcinogenic peroxisome proliferators significantly increase the mRNA levels of peroxisomal .beta.-oxidation genes in the rat liver by enhancing the transcriptional activity. Because of a good correlation between the inducibility of peroxisome proliferation and carcinogenicity of this class of xenobiotics, we proposed that sustained induction of peroxisomal .beta.-oxidation system and the resultant oxidative stress form the basis for carcinogenesis. Since this concept implies that tumors should develop only in tissues which display maximal peroxisome proliferation, we have now assessed the degree to which catalase and the three .beta.-oxidation genes are expressed in liver and 12 extrahepatic tissues of adult rats fed for 2 weeks a diet containing 0.025% ciprofibrate (w/w), a peroxisome proliferator. In the ciprofibrate-treated rats, the levels of catalase mRNA increased to < 2-fold in liver, kidney, intestine, and heart, but no change was detected in other tissues. The mRNA levels of the three genes of .beta.-oxidation system in the liver of adult rats treated with ciprofibrate increased > 20-fold. In contrast, in the kidney, small intestine, and heart the increases in the mRNA levels of all three .beta.-oxidation genes were small and varied from 2- to 4-fold following ciprofibrate treatment. Ciprofibrate did not significantly increase the levels of these mRNAs in the other nine tissues. These results correlated well with the levels of peroxisomal .beta.-oxidation activity, peroxisome volume density, and the immunologically quantified proteins in various tissues. These results provide evidence for the presence of .beta.-oxidation enzymes in peroxisomes of many tissues of rat and for tissue (cell)-specific differences in the inducibility of mRNAs of these .beta.-oxidation genes. The marked inducibility of .beta.-oxidation genes in liver and subsequent development of liver tumors support the hypothesis that tumors develop in tissues that show inducibility of peroxisome proliferation vis a vis .beta.-oxidation system following exposure to peroxisome proliferators.