OXIDATIVE DAMAGE TO NUCLEIC-ACIDS IN MOTOR-NEURONS CONTAINING MERCURY

Heavy metals have been implicated in the pathogenesis of sporadic moto r neuron disease (MND). We were interested to see if inorganic mercury leads to oxidative damage in motor neurons since free radicals have b een suspected to be involved in MND, so a method to examine oxidativel y-damaged DNA in situ was used to examine individual motor neurons. Mi ce were exposed to 500 mu g/m(3) of mercury vapour for 2 h. Two, five, or ten days later sections from formalin-fixed, paraffin-embedded blo cks of cervical spinal cord were incubated in avidin-FITC. Sections we re examined under a fluorescence microscope and photographs of pairs o f 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 contro l and mercury-exposed motor neurons. In each control-mercury pair (fou r pairs per group) significantly more perikaryal fluorescence was seen in mercury-containing than in control motor neurons (Mann-Whitney tes ting). Mercury within the motor neuron perikaryon therefore leads to i ncreased avidin binding, an indicator of oxidative damage to DNA. The findings support the hypothesis that an environmental toxin such as me rcury can enter and damage motor neurons. (C) 1998 Elsevier Science B. V. All rights reserved.