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 malonaldehyde 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 at 48 hr after treatment. These results suggest that the generation of oxidative products is related to the DNA damage produced by MPTP in mice.
Ortiz
Genaro G
GG
División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, CP 44340, Guadalajara, Jalisco, Mexico. genarogabriel@yahoo.com
Zúñiga-González
Guillermo
G
García
Joaquín J
JJ
Torres-Bugarín
Olivia
O
Zamora-Perez
Ana
A
Bitzer-Quintero
Oscar K
OK
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000818:Animals; D001769:Blood / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D015259:Dopamine Agents / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects*; D020267:MPTP Poisoning / Q000235:genetics / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D015162:Micronucleus Tests; D018384:Oxidative Stress
D015259:Dopamine Agents; D008315:Malondialdehyde; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine