PEROXISOME THROUGH CELL-DIFFERENTIATION AND NEOPLASIA

Peroxisomes are essential in cellular metabolism as their dysgenesis o r defects in single enzymes or impairment of multiple peroxisomal enzy matic functions have been found in several inherited metabolic disease s with serious clinical sequelae. The assembly and formation of these cytoplasmic organelles constitute a major and intringuing research top ic. In the present study the biogenesis of peroxisomes and the develop mental patterns of their enzymes have been reviewed during embryonic a nd/or post-embryonic ontogenesis of lower (amphibians) and higher (avi ans, mammals) vertebrates. In developing vertebrates, epithelial cell differentiation is accompanied by increases in frequency and size of p eroxisomes. The tissue-specific expression of peroxisomal enzymes cont ributes substantially to the biochemical maturation of epithelial cell s. The relationship between biogenesis of peroxisomes, expression of p eroxisomal enzymes and structural and functional cellular phenotype ha s also been investigated in differentiating epithelial cells along the crypt-villus axis of the adult rat intestine. Cytochemical studies at the ultrastructural level have provided evidence that peroxisomes are already present in proliferating cells of the intestinal crypt region before they begin to differentiate. Migration and differentiation of intestinal epithelial cells from crypt to villus compartments are mark ed by significant increases in number and size of catalase-positive st ructures. Increasing activity gradients from crypt to surface areas ar e found for the peroxisomal oxidases examined (enzymes of the peroxiso mal beta-oxidation system, D-amino acid oxidase and polyamine oxidase) . Thus, peroxisomes are more and more involved in oxidative metabolic pathways as intestinal epithelial cells differentiate. Finally, we hav e analyzed the peroxisomal behaviour in human neoplastic epithelial ce lls. The presence of peroxisomes has been cytochemically revealed in h uman breast and colon carcinomas. Peroxisomal enzyme specific activiti es are significantly lower in human breast and colon carcinomas than i n the adjacent healthy mucosa. Furthermore, a relationship is found be tween the specific activities of some peroxisomal enzymes and the hist ological tumour grades.