Disease relevance of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• At 14 days of age, male Lewis rats were each given injections of a single dose of 30 mg azaserine/kg body weight [1].
• Inbred W/LEW rats and noninbred CD-1 mice were compared for responsiveness to induction of pancreatic adenocarcinomas by azaserine [2].
• This study investigates digestive and lysosomal enzyme secretion of azaserine-induced pancreatic acinar carcinomas in response to cholecystokinin in rats [3].
• An acinar cell carcinoma of the pancreas, which was induced in a male Wistar rat by repeated injections of azaserine, was propagated in cell culture [4].
• It is concluded that (a) cholecystokinin plays a significant role in camostate-stimulated growth of acidophilic putative preneoplastic foci in rat pancreas and (b) CR-1409 inhibits growth of putative preneoplastic foci induced in rat pancreas by azaserine and hence may be of potential value for the treatment of pancreatic cancer in humans [5].

Psychiatry related information on (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• These results suggest that the reduction in the synthesis of PG-H as well as the production of an abnormal form of PG-H during a critical period of limb morphogenesis may be important factors in explaining the micromelia induced by azaserine [6].

High impact information on (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• Inhibition of GFAT by the substrate analogue azaserine or by inhibition of GFAT protein synthesis with antisense oligonucleotide prevented the high glucose-induced increase in cellular glucosamine metabolites and TGF-beta1 expression and bioactivity and subsequent effects on mesangial cell proliferation and matrix production [7].
• Effect of dietary omega-3 and omega-6 fatty acids on development of azaserine-induced preneoplastic lesions in rat pancreas [8].
• Fourteen-day-old animals were given a single ip injection of 30 mg L-azaserine/kg body weight [CAS: 115-02-6; diazoacetate serine (ester)] [9].
• Subtoxic doses of azaserine induced atypical acinar cell nodules (AACN) in the pancreases of outbred Wistar rats, inbred W/LEW and F344 rats, and outbred Charles River CD-1 albino mice 4-6 months after initiation of treatment in the growing animal [10].
• When both types of cell lines were cultured in a medium containing 0.4 microM methotrexate, 16 microM uridine, and 16 microM thymidine (or 10 microM azaserine alone), no cells grew [11].

Chemical compound and disease context of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• The attenuation of CCE was also seen with glucosamine, and the inhibition by hyperglycemia was prevented by azaserine, thereby implicating hexosamine biosynthesis as the responsible metabolic pathway [12].
• Adenine transport was also diminished in AE1 and FURD-80-3-6 cells, but not to sufficiently low levels to interfere with their ability to salvage adenine to overcome azaserine toxicity [13].
• The inhibition by hyperglycemia of phenylephrine-induced inotropy was reversed with azaserine and mimicked by glucosamine [12].
• Rats were given 25 weekly injections of 10 mg/kg body weight of azaserine and 1 mg/kg body weight of tetragastrin as a suspension in olive oil every other day [14].
• The improved survival with hyperglycemia was attenuated by azaserine, which inhibits glucose metabolism via the hexosamine biosynthesis pathway [15].

Biological context of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• To test whether the silent allele was activated via hypomethylation of genomic DNA, H23 cells were treated with inhibitors of DNA methylation, and revertants were scored by HAT or azaserine selection [16].
• DNA damage and repair in rat tissues following administration of azaserine [17].
• These results showed that estradiol treatment and the drop in testosterone levels caused by castration were highly effective in inhibiting the development and growth of preneoplastic lesions of the pancreas of the rats treated with azaserine [18].
• The tissue distribution of radioactivity following injection of a 14C-labeled sample is similar to that of azaserine; however, this compound is not a direct-acting bacterial mutagen [19].
• The burden of azaserine-induced foci was decreased by approximately 37%, and this was attributed to the well known effects of reduced caloric intake in these young, rapidly growing rats [20].

Anatomical context of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• The response of two rodents to azaserine carcinogenicity for the pancreas was evaluated [21].
• Feeding of raw soya flour or other trypsin inhibitors such as camostate is a well-established method for promoting growth of (pre)neoplastic foci induced in the exocrine pancreas of rats by azaserine [5].
• Furthermore, photolysis of azaserine in the presence of lymphocytes results in specific irreversible inhibition of L-system transport [22].
• We have found that the amino acid derivative, O-diazoacetyl-L-serine (azaserine), is a potentially useful probe for identification of the L-(leucine-favoring) system transporter in human T-lymphocytes [22].
• Administration of azaserine (250 micrograms) to day-4 chick embryos in ovo was shown to induce micromelial limbs [6].

Associations of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium with other chemical compounds

• After initiation with 30 mg/kg of azaserine, six groups of 15 Wistar rats were treated for 16 wk with cholecystokinin, bombesin, or gelatin (control), some in combination with CR-1409 [23].
• The incidence of pancreatic carcinoma among a male positive control group (azaserine treated, but not retinoid treated) was 42% [24].
• Inhibitory effects of estrogen and castration on the early stage of pancreatic carcinogenesis in Fischer rats treated with azaserine [18].
• Azaserine (AZA; 0.5 micromol/l), an inhibitor of GFA, blocks the HG- but not the GlcN-induced fibronectin synthesis [25].
• In addition, we found that glucosamine-induced desensitization did not require glutamine and was unaffected by azaserine treatment [26].

Gene context of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• In the present study, we investigated gastrin (CCK-B) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6, comparing it to normal rat pancreas, and we also characterized CCK receptor subtypes in this tumor [27].
• Overexpression of messenger RNA for cholecystokinin-A receptor and novel expression of messenger RNA for gastrin (cholecystokinin-B) receptor in azaserine-induced rat pancreatic carcinoma [28].
• Overexpression of either ydeD or yfiK leads to alleviation of this inhibition paralled by increased resistance to azaserine, which is an analog of O-acetylserine [29].
• In contrast, the azaserine-induced significant increase in hepatic putrescine was lower and transient, was accompanied by an increase in ODC and SAM-DC, and was completely inhibited by simultaneous DFMO treatment but not by MDL 72527 [30].
• S-Adenosylmethionine decarboxylase (SAM-DC) activity was significantly decreased in the pancreata of azaserine-treated animals compared to controls [30].

Analytical, diagnostic and therapeutic context of (E)-2-[(2S)-2-amino-2-carboxy-ethoxy]-2-hydroxy-ethenediazonium

• Chemoprevention by retinoids of the progression of carcinomas induced in rats by azaserine was evaluated [24].
• Animal model of human disease. Carcinoma of the pancreas in azaserine-treated rats [31].
• Gut peptides are involved in the growth and carcinogenesis of the exocrine pancreas of rats after treatment with azaserine [32].
• The present long-term (12 months) study was carried out to investigate the effects of Sandostatin (3 microgram/day), alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters [33].
• The number and size of pancreatic atypical acinar cell foci was significantly higher (P < 0.01) in azaserine-treated animals maintained on a high fat diet than in those fed a low fat diet [34].

References