The influence of di(2-ethylhexyl)phthalate on protein turnover in rat liver

Treatment of rats with the plasticizer di(2-ethylhexyl)phthalate increases liver weight and leads to proliferation of mitochondria and peroxisomes. Using in vivo labelling with [3H]leucine, an increased rate of incorporation into the total protein of mitochondria and microsomes was observed. The half-lives of proteins in subcellular fractions were determined using [35S]methionine labelling. The half-lives for the total protein of mitochondria, microsomes, and supernatant were increased from 6 to 25 days, from 3.5 to 5.5 days and from 2.5 to 5 days upon treatment with phthalate esters. Experiments with [14C]guanidino-L-arginine indicated that some reutilization of [35S]methionine occurred, but this did not influence the results substantially. It appears that phthalate esters increase protein synthesis and decrease protein breakdown, the former effect being of greater importance.