L-azaserine induced preneoplasia in the rat pancreas. A morphometric study of dietary manipulation (lipotrope deficiency) and ultrastructural differentiation.
Putatively preneoplastic, pancreatic atypical acinar cell foci (AACF) and nodules (AACN), collectively termed atypical acinar cell lesions (AACL), were induced in male Lewis rats by L-azaserine (300 mg/kg body weight [bw] in divided doses). Rats given carcinogen and then fed a lipotrope deficient (LD) diet developed a significantly greater number of larger lesions than animals fed complete diet throughout the experiment. It is suggested that lipotrope deficiency plays a promoting role in this model of pancreatocarcinogenesis. Ultrastructural morphometric studies of AACF, when compared to control tissues, revealed the following significant results: 1) a decrease in surface area of cell cytoplasm with no change in nuclear area, and hence increased nucleus/cytoplasm (N/C) ratio; 2) a reduction in size and uniformity of zymogen granules; and 3) an increase in number of granules per microns 2 of cell. The results suggest that arrested development of the AACF cells is associated with reduced cytoplasm and zymogen production per cell. AACL may be eosinophilic due to an overall increased concentration of zymogen in these hyperplastic lesions and not because individual acinar cells in the AACL contain an increased amount of zymogen or are "zymogen-rich," as has been reported.
Andry
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Mallory Institute of Pathology, Boston, Massachusetts 02118.
Kupchik
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Rogers
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D000818:Animals; D001377:Azaserine / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D002796:Choline Deficiency / Q000150:complications; D003594:Cytoplasmic Granules / Q000032:analysis / Q000648:ultrastructure; D004032:Diet; D004792:Enzyme Precursors / Q000032:analysis; D005494:Folic Acid Deficiency / Q000150:complications; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000172:deficiency; D008854:Microscopy, Electron; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology* / Q000648:ultrastructure; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew; D014806:Vitamin B 12 Deficiency / Q000150:complications; D008083:beta-Lipotropin / Q000172:deficiency
D004792:Enzyme Precursors; D001377:Azaserine; D008083:beta-Lipotropin; D008715:Methionine