Collagen accumulation can continue with decreased prolyl hydroxylase activity in the liver.

A single dose of dimethylnitrosamine dose-relatedly increased total hepatic hydroxyproline content in rats 14 days after the dosing. In cases of 35 mg/kg of dimethylnitrosamine, it increased rapidly to 1.7 times the normal level within 14 days. This increase persisted thereafter until 84 days. Hepatic collagen prolyl hydroxylase activity was 1.8 times the normal level by the fourth day after the dosing but normalized within 14 days. It decreased further to levels significantly lower than those in normal rats at 28, 56 and 84 days. Serum glutamic pyruvic transaminase activity was about 13 times the normal level at 2 days and normalized after 7 days. On histology, fiber developed in necrotic areas around the central veins after 7 days and remained after 28 days when the necrosis had already disappeared. These results suggest that abnormal collagen can continue to increase in the state of decreased collagen prolyl hydroxylase activity in the liver.