ROLE OF APOPTOSIS IN COPPER DEFICIENCY INDUCED PANCREATIC INVOLUTION IN THE RAT

Rats maintained on a copper-deficient diet supplemented with a copper- chelating agent, triethylenetetramine tetrahydrochloride, for 8 to 10 weeks show marked involution of pancreatic acinar tissue. The present study deals with the possible mechanism of pancreatic acinar cell invo lution during copper deficiency. Sequential light and electron microsc opic observations during the copper-depletion regimen, suggest that ap optosis is the main cause of progressive loss of acinar cells. At 4 we eks of copper deficiency, the apoptotic index was 2 +/- 0.6/1,000 cell s. By 6 weeks, the apoptotic index reached a maximum of 95 +/- 25/1,00 0. By 8 weeks, there was almost total loss of acinar cells. The earlie st change of apoptosis was characterized by condensation and marginati on of chromatin against nuclear membrane. Subsequently, several apopto tic bodies displayed pyknotic nucleus and eosinophilic cytoplasmic con densation. Apoptotic bodies were extruded into the interstitium or pha gocytosed by unaffected acinar cells. No associated pancreatic inflamm ation was present. These results indicate that apoptosis is the proces s involved in pancreatic involution caused by copper deficiency. The m olecular mechanism(s) by which copper deficiency causes apoptosis rema in unclear.