TOXICITY AND CHEMICAL FORM OF SELENIUM IN THE LIVER OF MICE ORALLY-ADMINISTERED SELENOCYSTINE FOR 90 DAYS

The subacute oral toxicity of selenocystine and chemical form of selen ium in the liver following exposure to this compound were assessed in ICR male mice. Animals were dosed 6 days/week for 30, 60 or 90 days wi th 0, 5, 10 or 15 mg/kg per day. Body weight gain decreased with dosag e. The activities of aspartate aminotransferase and alanine aminotrans ferase in plasma were significantly elevated at the highest dose level after 60 days and at the two higher dose levels after 90 days of expo sure. However, the level of selenium content in the liver was the same at the two higher dosages at both 60 and 90 days of exposure. The sub cellular distribution of selenium in the liver from mice treated with selenocystine showed that the major part of the total selenium content , 68.3-72.1%, existed in the cytosolic fraction. Sephadex G-150 chroma tograms of liver cytosol of the animals administered selenocystine rev ealed three selenium-containing fractions which involve glutathione pe roxidase (molecular weight 80 000) high molecular (molecular weight 55 000- 60 000) and low molecular (molecular weight < 10 000) substances . Selenium content and acid-volatile selenium content in the high mole cular weight fraction increased with exposure time to selenocystine. T hus, in a subacute toxicity study selenocystine given for 90 days caus ed hepatic damage in mice, depending on the acid-volatile selenium con tent in the liver cytosol.