UNUSUAL GENERATION OF HYDROXYL RADICALS IN HEPATIC COPPER-METALLOTHIONEIN OF LEC (LONG-EVANS CINNAMON) RATS IN THE PRESENCE OF HYDROGEN-PEROXIDE

A mutant strain of LEC rats (Long-Evans rats with a cinnamon-like coat color) develop spontaneous hepatic injury associated with severe jaun dice about 4 months after birth. Recently, we obtained evidence which shows an unusual accumulation of copper (Cu) in the liver of LEC rats, followed by the finding of copper-methallothionein (Cu-MT) induction. To know the mechanism for the development of hepatitis in LEC rats, i n relation to induced Cu-MT, we examined whether the generation of act ive oxygen species is observed. When the Cu-MT was treated with H2O2, which is formed by dismutation of superoxide anion radicals or NADPH o xidases in living systems, strong ESR signals due to Cu(ll) state appe ared when measured at 77K. On the same system, ESR signals due to the spin trapped hydroxyl radicals were observed at room temperature when DMPO (5,5-dimethyl-pyrroline-l-oxide) was used as a spin-trapping agen t. The present results suggested that Cu-MT of LEC rat has an importan t pathogenic role by generating hydroxyl radicals, when hydrogen perox ide is produced in cells or tissues. (C) 1994 Academic Press, Inc.