HISTOCHEMICAL DETERMINATION OF STEREOSELECTIVITY OF ESTERASES IN NORMAL PANCREAS AND PANCREATIC TUBULAR ADENOCARCINOMA OF HAMSTERS

Esterases in normal hamster pancreas and pancreatic tubular adenocarci noma of ductal origin induced by N-nitrosobis(2-oxopropyl)amine were s tained in cryostat sections with mixtures of a diazonium salt (fast bl ue RR) and with each of the enantiomers of alpha-naphthyl N-methoxycar bonylalaninate, N-methoxycarbonylvalinate, and N-acetylprolinate. Azo coupling of alpha-naphthol formed by enzymatic hydrolysis with the dia zonium, salt gives an azo dye that indicates the presence and amount o f the enzyme activity in situ, Comparison between the color intensitie s obtained with each of the enantiomers of a chiral alpha-naphthyl est er shows the stereoselectivity, or enantiomeric preference, of the enz yme, Esterases in acinar cells of the normal pancreas showed slight st ereoselectivity for N-methoxycarbonylalaninate, while esterases in fat cells scattered throughout the exocrine pancreas showed high stereose lectivity for (R)-N-acetylprolinate. These esterase activities were no t found in the turner, but another prominent esterase activity with hi gh stereoselectivity for (S)-N-methoxycarbonylvalinate was found, Simi lar results were Obtained by staining after polyacrylamide gel electro phoresis showing that the bands of esterases in the adenocarcinoma sta ined only with the S enantiomer of the N-methoxycarbonylvalinate, The present method is a valuable tool for designing anticancer prodrugs th at are activated by tumor-specific esterases.