Oxidative damage to nucleic acids in motor neurons containing mercury.
Heavy metals have been implicated in the pathogenesis of sporadic motor neuron disease (MND). We were interested to see if inorganic mercury leads to oxidative damage in motor neurons since free radicals have been suspected to be involved in MND, so a method to examine oxidatively-damaged DNA in situ was used to examine individual motor neurons. Mice were exposed to 500 microg/m3 of mercury vapour for 2 h. Two, five, or ten days later sections from formalin-fixed, paraffin-embedded blocks of cervical spinal cord were incubated in avidin-FITC. Sections were examined under a fluorescence microscope and photographs of pairs of mercury-exposed and control spinal motor neurons were analysed semi-quantitatively for the amount of fluorescence using an image analysis program. Avidin fluorescence was seen in the perikaryon of both control and mercury-exposed motor neurons. In each control-mercury pair (four pairs per group) significantly more perikaryal fluorescence was seen in mercury-containing than in control motor neurons (Mann-Whitney testing). Mercury within the motor neuron perikaryon therefore leads to increased avidin binding, an indicator of oxidative damage to DNA. The findings support the hypothesis that an environmental toxin such as mercury can enter and damage motor neurons.
Pamphlett
R
R
Department of Pathology, The University of Sydney, New South Wales, Australia. rogerp@pathology.usyd.edu.au
Slater
M
M
Thomas
S
S
D000818:Animals; D001360:Avidin / Q000031:analogs & derivatives; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D008628:Mercury / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D005456:Fluorescent Dyes; D009696:Nucleic Acids; D001360:Avidin; D008628:Mercury; D016650:Fluorescein-5-isothiocyanate