Effect of disturbing endocrine drug, DEHP, on microcyst formation in the epithelial cells.

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Vacuolar H^+-ATPase(V-ATPase) is localized in organelles of the central vacuolar system such as lysosomes, coated vesicles, and the Golgi apparatus, and it plays an important role in maintaining the acidic enviroment in these compartments. We investigated the effects of di(2-ethylhexyl) phthalate (DEHP) on mouse liver lysosomes. After 2-3 weeks of oral administration in mice, a reduction in vacuolar H^+-ATPase, as determined by immunocytochemical analysis. When the mice were subsequently fed a normal diet for 1 week, V-ATPase, levels recovered to normal values. According to Northern blot analysis, V-ATPase subunit A mRNA decreased gradually with DEHP treatment. Enzyme cytochemical staining showed acid phosphatase to be present in lysosomes and late autophagosomes in normal animals as well as in DEHP-treated animals. But the number of late autophagosomes containing acid phosphatase increased clearly after DEHP treatment. These results suggest that, DEHP causes marked V-ATPase reduction in the liver lysosomal compartment and the effect to DEHP is reversible, and the effect of DEHP on protein expression is likely to be exerted at the transcriptional level. Thus in this study, we report that DEHP treatment causes a reduction in V-ATPase subunit A in the liver lysosomal compartment, which may accent for the inability to degrade excess cell organelles.