DOPAMINE-INDUCED PROGRAMMED CELL-DEATH IN MOUSE THYMOCYTES

Exposure of mouse thymocytes to dopamine caused apoptosis (programmed cell death). This was manifested by cellular condensation and membrane damage shown by flow cytometry measurements and scanning electron mic roscopic study. Dopamine also affected thymocytic nuclei and their gen omic DNA integrity. Most of the DNA molecules accumulated in a subdipl oid peak in flow cytometry analysis, indicating DNA fragmentation to s mall particles. DNA analysis showed the typical pattern of 'DNA ladder ' caused by internucleosomal DNA cleavage. X-ray microanalysis of the cellular elements of dopamine-treated cells showed elevation of sodium (Na), chloride (Cl) and calcium (Ca) peaks, accompanied by reduction in phosphate (P) concentrations. Comparison of the potassium (K) and P concentrations showed significant differences between the two major d eath processes: necrosis (induced by exposure to sodium azide (NaN3)) and apoptosis (induced by dopamine). High concentrations of K indicate d cell viability while reductions in P and elevations in Ca levels wer e found to be typical of apoptotic cell death. The antioxidant dithiot hreitol (DTT) suppressed dopamine-induced apoptosis in thymocytes, sug gesting that its toxicity may be mediated via generation of reactive o xygen radicals. Our study suggests that under certain circumstances, d opamine and/or its metabolites, may induce a process of apoptotic cell death of the dopamine-producing cells in the substantia nigra. Increa sed accessibility of dopamine to the nigral cell nucleus or inability to scavenge excess free radicals generated from dopamine oxidation tri ggering programmed cell death, may cause the progressive nigral degene ration in Parkinson's disease.