Pancreatic Islet Cell Tumors Produced by the Combined Action of Streptozotocin and Nicotinamide

Rakieten, Nathan; Gordon, Benjamin S.; Beaty, Annabel; Cooney, David A.; Davis, Ruth D.; Schein, Philip S.

doi:10.3181/00379727-137-35561

Cited by 116 publications

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“…Rat B-cell tumor was induced with streptozotocin and nicotinamide [7]. The tumors were produced in almost all (90-95 %) of the male Wistar rats treated with these two agents.…”

Section: Preparation Of Rat B-cell Tumormentioning

confidence: 99%

“…induced by streptozotocin and nicotinamide can be used as a suitable material for isolation and purification of proinsulin mRNA, since the RNA from the tumor was found to be highly active in stimulating the incorporation of [3H]leucine into preproinsulin in the wheat germ cell-free protein-synthesizing system, and since the tumor can be easily produced in rats [7]. Further, more recently we have demonstrated that the induction of proinsulin synthesis by glucose in rat pancreatic islets is controlled at the translational level [8,9].…”

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confidence: 99%

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Purification and Characterization of Proinsulin mRNA from Rat B‐Cell Tumor

Itoh

Nose

Okamoto

1979

European Journal of Biochemistry

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Proinsulin mRNA was purified from rat B-cell tumor induced by streptozotocin and nicotinamide. The purification was achieved through the use of oligo(dT)-cellulose chromatography and sucrose gradient centrifugation. As judged by translational activity in a cell-free protein-synthesizing system of wheat germ, proinsulin mRNA was purified 362-fold from total nucleic acid of the B-cell tumor. Purified proinsulin mRNA migrated as a single symmetrical peak on sucrose gradient centrifugation and as a single band on polyacrylamide gel electrophoresis in the presence of formamide. The translation product of purified proinsulin mRNA in the cell-free protein-synthesizing system was found to be only preproinsulin, as analyzed by dodecylsulfate/polyacrylamide gel electrophoresis and immunoprecipitation.The molecular weight of proinsulin mRNA, determined by polyacrylamide gel electrophoresis in the presence of formamide, was approximately 200 000 (equivalent to approximately 570 nucleotides). Almost all of the proinsulin mRNA was bound to oligo(dT)-cellulose, and the translation of proinsulin mRNA in a cell-free protein-synthesizing system of wheat germ was completely inhibited by 7-methylguanosine 5'-phosphate. These results indicated that the nucleotide sequences in proinsulin mRNA consisted of 58 "/, translatable sequences and 42 % untranslatable sequences, presumably containing a capped structure, a 7-methylguanosine residue, at the 5' terminus and a poly(A) sequence at the 3' terminus.The translation product of purified proinsulin mRNA, preproinsulin, was found to consist of two types of preproinsulin I (57 %) and preproinsulin I1 (43 %). This result indicated that the isolated proinsulin mRNA consisted of two types of proinsulin I mRNA and proinsulin I1 mRNA in approximately equal amounts.Complementary DNA was synthesized with proinsulin mRNA as a template. From the experiment of hybridization kinetics under conditions of excess RNA, the ~g f l , Z of proinsulin mRNA was found to be 2.1 x moll-' s. This result also confirmed that proinsulin mRNA had been isolated in a high degree of purity.The investigation of the mechanisms controlling transcription and translation in eukaryotic cells have been facilitated by the isolation of specific mRNAs [I -31. Purified mRNA can be employed as a template for the synthesis of complementary DNA and in investigation of mRNA structure and function.In recent years several attempts have been carried out to isolate and characterize proinsulin mRNA from mammalian and fish pancreatic islets and from an X-ray-induced islet tumor. However, because of the limited availability of these materials, proinsulin mRNA has been only partially purified [4,5]. In the preceeding paper [6] we reported that the B-cell tumor -.Ahhreviutions. Hepes, 4-(2-hydroxyethyI)-l-piperazineethanesulphonic acid; Tos-Phe-CHzCI, L-1-tosylamido-2-phenylethyl chloromethyl ketone.induced by streptozotocin and nicotinamide can be used as a suitable material for isolation and purification of proinsulin mRNA, since the RNA fr...

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“…Rat B-cell tumor was induced with streptozotocin and nicotinamide [7]. The tumors were produced in almost all (90-95 %) of the male Wistar rats treated with these two agents.…”

Section: Preparation Of Rat B-cell Tumormentioning

confidence: 99%

mentioning

confidence: 99%

Purification and Characterization of Proinsulin mRNA from Rat B‐Cell Tumor

Itoh

Nose

Okamoto

1979

European Journal of Biochemistry

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“…It is well known that SZ induces insulinoma [4,6,9,15,20] and renal tumor [1,16,17] in a high incidence in rats 8-9 months or more after single injection. However, there have been few reports on the induction of other tumors by SZ administration in laboratory animals.…”

Section: Streptozotocinmentioning

confidence: 99%

Neoplastic Lesions in Streptozotocin-treated Rats

Okawa

Doi

1983

Experimental Animals

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Pathological examination was carried out on 16 male Sprague-Dawley rats received single i. v. injection of 60 mg/kg of streptozotocin (SZ) at 5 weeks of age and maintained for 22 months. Insulinoma (63 %), renal adenoma (50 %), hepatocellular tumor (69 %), cholangioma (31 %) and Leydig cell tumor (56 %) were found in a high incidence, and therefore occurrence of these tumors was considered to be attributable to the treatment with SZ. In addition to these tumors, though in a low incidence, various such tumors as leukemia, reticulum cell sarcoma, mammary tumor and glioma were also found.

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“…It is known that STZ induces strand breaks in different cell types including beta cells [20] and that it can also activate oncogenes, such as H-ras oncogene [21]. STZ can induce tumour growth in islets, kidney, liver, and mammary gland [22,23]. Complex effects of STZ including DNA damage on beta cells have been extensively reported.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

et al. 1993

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Summary. Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of diabetic parents in both strains. Group 1 consisted of litters from control mice with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and a control father, group 3 litters had control mother with LDS diabetic father, and group 4 litters had both, LDS diabetic mother and father. Diabetes was induced by 5 x 40 mg streptozotocin per kg on five consecutive days. Progeny of diabetic mothers showed a state of reduced glucose tolerance associated with reduced glucose disappearance during intravenous glucose tolerance test and increased insulin secretion of isolated islets of Langerhans. These metabolic abnormalities predominated in the male litters of both strains of mice. Amniotic insulin was increased ~n diabetic mothers during pregnancy. No histologic abnormalities were observed in group 2 progeny. Pancreases in male offspring of LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was found in 40 % of mice with normal glucose tolerance. A single subdiabetogenic dose of streptozotocin (40 mg/kg) induced insulitis in 90 % of pancreases accompanied by reduced insulin release of isolated islets. By contrast, male Balb/cHan progeny of diabetic fathers failed to develop insulitis. In conclusion, we found (1) parental LDS diabetes was transmitted more often to male offspring, (2) maternal LDS diabetes was associated with hyperinsulin secretion and glucose intolerance in the offspring and (3) paternal LDS diabetes was accompanied by insulitis and insulin secretion deficiency in CD-1 progeny.

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Pancreatic Islet Cell Tumors Produced by the Combined Action of Streptozotocin and Nicotinamide

Cited by 116 publications

References 0 publications

Purification and Characterization of Proinsulin mRNA from Rat B‐Cell Tumor

Purification and Characterization of Proinsulin mRNA from Rat B‐Cell Tumor

Neoplastic Lesions in Streptozotocin-treated Rats

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

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