INDUCTION BY MERCURY-COMPOUNDS OF BRAIN METALLOTHIONEIN IN RATS - HG-0 EXPOSURE INDUCES LONG-LIVED BRAIN METALLOTHIONEIN

Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to m ost heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and caus e neurological damage. Rats treated with MeHg (40 mu mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 mu g/g with slight neurological signs 10 days after final administration, but brain MT le vels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 mu g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Althou gh brain Hg levels fell gradually with a half-life of 26 days, MT leve ls induced by Hg exposure remained unchanged for >2 weeks. Gel fractio nation revealed that most Hg was in the brain cytosol fraction and thu s bound to MT. Hybridization analysis showed that, despite a significa nt increase in MT-I and -II mRNA in brain, MT-III mRNA was less affect ed. Although significant Hg accumulation and MT induction were observe d also in kidney and liver of Hg vapor-exposed rats, these decreased m ore quickly than in brain. The long-lived MT in brain might at least p artly be accounted for by longer half-life of Hg accumulated there. Th e present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT.