Differential effects of dopaminergic neurotoxins on DNA cleavage.
OBJECTIVE
Environmental and endogenous toxins are considered to increase the risk of dopaminergic neurodegeneration. Parkinson's disease is a neurological disorder occurring due to the death of dopaminergic neurons in substantia nigra. The present study investigated the effect of parkinsonian neurotoxins salsolinol and rotenone on plasmid and genomic DNA.


METHODS
Salsolinol or rotenone (0-1000 μM) alone or in presence of divalent metals (copper or iron) was incubated with plasmid DNA pBR322 (1 μg) or calf thymus DNA (1 μg). In order to study their effects on restriction endonuclease sites, the plasmid DNA was incubated with the neurotoxins (salsolinol or rotenone), extracted and subjected to restriction enzyme digestion (BamHI, EcoRV, HindIII, SalI).


RESULTS
Exposure of rotenone or salsolinol alone to the plasmid or calf thymus DNA did not induce any strand scission or damage. However, salsolinol in the presence of divalent copper induced strand scission and damage in both plasmid and genomic DNA. All of the tested restriction endonucleases linearized the plasmid DNA pre-treated with salsolinol or rotenone suggesting that these neurotoxins did not selectively damage the restriction enzyme sites in the DNA.


CONCLUSIONS
The above observations suggest that salsolinol and rotenone differentially interact with DNA in inducing damage in the presence of copper, and behave similarly in their binding to DNA by not damaging the selected restriction endonuclease cleavage sites.


CONCLUSIONS
Risk for neuronal degeneration can be significantly augmented by the environmental and endogenous toxins in the presence of various metals due to their deleterious effects on DNA.
Plummer Movement Disorders Center, Department of Neurology, Scott & White Clinic, Temple, Texas, USA.
Binu
B
Tharakan
Muralikrishnan
M
Dhanasekaran
Bala V
BV
Manyam
D000818:Animals; D002417:Cattle; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D053837:DNA Cleavage / Q000187:drug effects*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D016678:Genome / Q000187:drug effects; D007501:Iron / Q000494:pharmacology; D007546:Isoquinolines / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D010957:Plasmids / Q000187:drug effects; D012402:Rotenone / Q000633:toxicity*
D007546:Isoquinolines; D009498:Neurotoxins; D012402:Rotenone; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; C036617:salsolinol; D007501:Iron