CuZn - superoxide dismutase ( CuZnSOD ) transgenic mice show

_, We have used female and male transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) , superoxide dismutase (SOD) gene in order to assess the lethal effects of methylenedioxyamphetamine (MDA) and methylene,_ im dioxymethamphetamine (MDMA). In contrast to non-Tg mice, both heterozygous and homozygous SOD-Tg mice showed resistance to the lethal effects of both drugs. Females of both SOD-Tg and non-Tg strains were somewhat more resistant to the _? ;._ effects of these drugs in comparison to males. In general, homozygous animals show greater resistance to the effects of the two ,, drugs. These results suggest that the acute lethal effects of amphetamine-substituted analogs might involve the intracellular '.i overproduction of the superoxide radicals secondary to hypoxic injury. The gender differences suggest that there might be _' 4 hormonal-free radical scavenger interactions that offer better protection to female mice. This might be related both to the _l _ lifespan of and to the lower prevalence of Parkinson's disease in women. Future studies will need to address these issues further. 3