Disease relevance of SMYD1

• Pilocarpine hydrochloride (PH) was administered as a single sc injection (15 mg/kg body wt) to outbred Syrian golden hamsters either prior to, simultaneously with, or after a single 20-mg/kg body weight dose of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) [1].
• The possible effects of dietary protein on pancreatic cancer induced in outbred Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) were studied [2].
• The incidence of ductular adenocarcinomas increased in both males and females (LF diet, 16%; HF diet, 34%) when the HF diet was fed after BOP treatment [3].
• The carcinogenicity of SZ for the exocrine pancreas was further indicated by induction of ductular carcinomas by SZ plus BOP, the incidence of which was significantly higher (P less than .0001) than that induced by BOP alone [4].
• Pancreatic adenoma yields were elevated in hamsters given either HF or HP diets following BOP treatment, by comparison with the low levels [5].

High impact information on SMYD1

• Syrian golden hamsters were fed four diets in experiments designed to evaluate the effects of the interaction of dietary fat and protein on carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4] [6].
• At 8 weeks, they were given injections sc of 10 mg BOP/kg body weight and placed on a control diet [9 g corn oil (medium fat) and 18 g casein (medium protein)/385 kcal] [6].
• The incidence of biliary cystic adenomas was highest in male hamsters that received HF diets, irrespective of BOP treatment, and BOP treatment resulted in increased yields of this lesion in females only in groups given HF-LP diet.(ABSTRACT TRUNCATED AT 400 WORDS)[6]
• BOP-induced lesions in the lungs, liver, common bile duct, gallbladder, and kidneys are described; results in the pancreas were reported separately [6].
• Survivors were killed 46 weeks after BOP administration, and the pancreas, common duct, and gallbladder were examined histologically [7].

Chemical compound and disease context of SMYD1

• N-Nitrosobis(2-oxopropyl)amine (BOP), a further postulated beta-metabolite of di-n-propylnitrosamine, induced a high incidence of pancreatic duct adenomas and adenocarcinomas as early as 13 weeks in Syrian hamsters receiving weekly sc injections for life and a few pancreatic adenomas, after 28 weeks, in those given a single sc dose [8].
• As with BOP, HPOP induced a higher incidence of pancreatic ductular adenocarcinomas than did N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine, and these neoplasms showed a great tendency for invasion and metastasis [9].
• Alloxan, when given intravenously at a dose of 60 mg/kg body weight 2 hours prior to subcutaneous injection of the potent pancreatic carcinogen N-nitrosobis (2-oxopropyl) amine (BOP), inhibited the induction of hyperplastic and neoplastic pancreatic lesions in a statistically significant fashion (P less than 0.01) [10].
• The total numbers of pancreatic lesions including carcinomas, atypical ductal hyperplasias and ductal hyperplasias and ductular proliferations in the liver were also significantly decreased in animals receiving BOP followed by 2% BHA [11].
• We report 30 hematologic malignancies arising in 25 of 236 Syrian golden hamsters (SGH) that received combinations of N-nitrobis(2-oxopropyl)amine (BOP) and Streptozotocin (STZ) [12].

Biological context of SMYD1

• Pregnant Syrian hamsters (F0 generation) were treated with BOP (10 mg/kg body weight) at the 8th, 10th, 12th, and 14th days of gestation (for a total dose of 40 mg/kg body weight) [13].
• These data indicate that BOP carcinogenesis is mediated through blood circulation, and that cancer development is not inhibited in the duct-excised lobe for up to 3 days after surgery [14].
• BOP and BHP were weak mutagens in the Salmonella/S-9 mutagenesis assay using hamster liver S-9 fraction [15].
• These findings indicated that etodolac reduced both the occurrence of severe cholangitis and the acceleration of biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of BOP-induced biliary carcinogenesis in hamsters [16].
• The results thus suggest that metabolic activation with STase is involved in BOP-induced pancreatic ductal carcinogenesis in hamsters, and support the hypothesis that BOP is metabolized to beta-hydroxyalkylnitrosamines followed by activation to proximate sulfuric acid esters by HSTase [17].

Anatomical context of SMYD1

• The results suggest that MNCO affects both acinar and ductal cells in the hamster and that the response of the hamster pancreas to MNCO and BOP is similar in many respects [18].
• No effects on tumor induction were seen in the pancreas or in other BOP target tissues (e.g., the common duct and gallbladder), whether E was given immediately after or 4 weeks before and immediately after BOP [19].
• Compared to related compounds, N-nitrosobis(2-hydroxypropyl)amine and N-nitrosobis(2-acetoxy-propyl)amine which are also pancreatic carcinogens, BOP induced only a few neoplasms of the lung, liver, and kidney and none in the nasal cavity, larynx, and trachea [8].
• However, HPOP [unlike BOP, but like N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine] led to tumor development in the nasal cavity, larynx, trachea, intestine, Harderian gland, lips, and flank organ [9].
• Based on the amount of protein in hepatic cytosol and endoplasmic reticulum, the two enzymes may be involved to a similar extent in the reduction of BOP to HPOP in the liver [20].

Associations of SMYD1 with chemical compounds

• Diets containing low-fat (LF) or high-fat (HF) levels of corn oil [4.5 or 18.0 g/385 kilocalorie (kcal)], contributing 10 or 41% of the calories, respectively, were fed either before or after a single injection of N-nitrosobis(2-oxopropyl)amine (BOP) (10 mg/kg body wt) [3].
• The first is a reductase associated with microsomes which reduces BOP to HPOP in the presence of reduced nicotinamide adenine dinucleotide at a rate of 9.1 nmol/min/mg of protein [20].
• Since both pancreatic carcinogens N-nitroso-2,6-dimethylmorpholine and BOP are metabolized to HPOP in the liver at rates much higher than those observed in the target organ pancreas, it is suggested that the liver may play an important role in pancreatic carcinogenesis in the hamster by these compounds [20].
• BOP administration 2 weeks after alloxan treatment, at which time pancreatic islet cell regeneration is considered completed, did not alter either the incidence or number of lesions [10].
• Exposure of hamsters to 5 daily doses of 20 mg/kg N-nitrosobis(2-oxopropyl)amine (BOP) or 76 mg/kg N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), resulted in reduced insulin secretion in freshly isolated pancreatic islets [21].

Analytical, diagnostic and therapeutic context of SMYD1

• Average tumor weight of animals in all peptide-treated groups, sacrificed 60 days after beginning the peptide treatment, was significantly lower than that of BOP controls [22].
• Pancreatic tumors were found in 89% of the BOP-treated F0 generation and in 5 (50%) of their male litters, but none was seen in their female progeny or in any hamsters from the F1 control group [13].
• Animals were treated with a single dose (20 mg/kg body weight) of N-nitrosobis(2-oxopropyl)amine (BOP) either immediately (Group 1) or on Days 1 (Group 2), 3 (Group 3) or 7 (Group 4) after ligation and excision of the duct of the splenic lobe [14].
• Group 5 received BOP shortly after laparoscopy, and Group 6 consisted of BOP-treated controls [14].
• Additional groups consisted of animals with PP alone (Group 4), sham operation (laparotomy) followed 30 minutes later by BOP treatment (Group 5), and BOP treatment only (Group 6) [23].

References