1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lipid peroxidation and DNA damage in mouse bone marrow and blood

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces Parkinsonism in humans, monkeys, and mice and oxidative stress in mammalian cells and tissues. In the present study, the relationship between the generation of lipid peroxidation products and DNA damage was studied in mice treated with MPTP. The frequency of micronucleated polychromatic erythrocytes (MN-PCE) and the concentrations of malonalclehyde and 4-hydroxyalkenals were determined in the bone marrow and peripheral blood of mice 0, 24, 48, 72, and 96 hr after treatment with MPTP, cyclophosphamide as a positive control, or diluent. Both MN-PCE and the lipid peroxidation products increased in MPTP-treated mice, with significant levels being detected in bone marrow starting at 24 hr after treatment and in blood starting of 48 hr after treatment. These results suggest that the generation of oxidative products is related to the DNA damage produced by MPTP in mice. (C) 2003 Wiley-Liss, Inc.