Article

Dieldrin elicits a widespread DNA repair and antioxidative response in mouse brain.

Department of Neurology, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA.
Journal of Biochemical and Molecular Toxicology (Impact Factor: 1.32). 02/2007; 21(3):125-35. DOI: 10.1002/jbt.20165
Source: PubMed

ABSTRACT Dieldrin is an organochlorine pesticide that is toxic for monoaminergic neurons. This study was designed to test the hypothesis that a weak DNA repair response to dieldrin by nigrostriatal dopaminergic (DA) neurons results in depletion of striatal DA. The activity of the mammalian base excision repair enzyme oxyguanosine glycosylase was utilized as the index of DNA repair. Other measures of oxidative stress were also studied, including the regional distribution of lipid peroxidation and superoxide dismutase (SOD) activity. The effects of acute and slow infusion of dieldrin on striatal DA levels were biphasic with a transient initial depression followed by increases beyond normal steady-:state levels. Dieldrin administration caused a global oxidative stress evidenced by increased levels of lipid peroxidation in all brain regions, an effect consistent with its capacity to affect mitochondrial bioenergetics. Dieldrin also elicited strong antioxidative and DNA repair responses across the entire mouse brain. Although mitochondrial SOD was not as increased in midbrain as it was in other regions following a cumulative dose of 24 mg/kg, this response, along with the robust DNA repair response, appeared to be sufficient to protect potentially vulnerable DA neurons from cytotoxicity. However, the long-:term consequences of chronic low-:dose dieldrin exposure remain to be studied, especially in light of the concept of "slow excitotoxicity,'' which postulates that even a mild bioenergetic compromise can over time result in the demise of neurons.

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    • "To identify cell processes impacted by dieldrin in the hypothalamus, sexually mature male LMB were fed a diet that contained 2.95 mg dieldrin/kg feed (measured) during a 2-month subchronic feeding study. It has been acknowledged that long-term consequences of chronic low concentration dieldrin exposure are not well studied (Sava et al., 2007), and this study contributes to a better understanding of how environmental exposures may lead to neuronal damage. In this study, LMB were fed a contaminated diet that would result in dieldrin tissue burdens comparable with levels in LMB found in sites with significant sediment contamination. "
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    • "Dieldrin has been previously shown to induce DNA repair mechanisms in mammals. Male mice i.p. injected with either 6 or 30 mg/kg dieldrin and treated between 6–72 h showed significant increases in the activity of 8-oxoguanine DNA glycosylase, an enzyme that repairs oxidatively damaged guanosine nucleotides (Sava et al., 2007). In the LMB hypothalamus, there appears to be a dynamic genomic response that includes both processes of DNA damage and repair/regeneration mechanisms. "
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