Disease relevance of Nitrosodiethylamine

• When the ascitic forms of two antigenically distinct guinea pig hepatomas induced by diethylnitrosamine are treated in vitro with chemotherapeutic drugs, their sensitivity to killing by xenogeneic antibody plus guinea pig complement increases [1].
• In A, after tracheas from 3-week-old untreated donor offspring were implanted into their mothers, the mothers received 18 mg diethylnitrosamine (DEN)/kg body weight, sc, twice weekly for 20 weeks [2].
• Liver neoplasms were induced in medakas (Oryzias latipes) by the addition of diethylnitrosamine (DENA) to their aquarium water at levels of 15-135 ppm for 8 weeks [3].
• Carcinomas developed in the mucosa of the esophagus in BUF strain rats ingesting diethylnitrosamine in the diet [4].
• Adenocarcinoma of the glandular stomach following 3-methylcholanthrene, N-nitrosodiethylamine, or N-nitrosodimethylamine feeding in carcinogen-susceptible inbred Syrian [5].

Psychiatry related information on Nitrosodiethylamine

• We now report for the first time that PH can also increase the tumour incidence, and decrease the latency period, when it is performed 8-10 weeks before treating rats with the hepatocarcinogen N-nitrosodiethylamine [6].
• Neonatal B6C3F1 mice were given a single carcinogenic dose of diethylnitrosamine (DEN) and the time-response kinetics for the early (foci of alteration) and late (adenomas/carcinomas) phases of hepatocellular carcinogenesis were compared to changes in hematopoiesis and immune functions associated with immune surveillance and natural resistance [7].

High impact information on Nitrosodiethylamine

• Surprisingly, mice lacking IKKbeta only in hepatocytes (Ikkbeta(Deltahep) mice) exhibited a marked increase in hepatocarcinogenesis caused by diethylnitrosamine (DEN) [8].
• Conditionally deleted Foxm1b mouse hepatocytes fail to proliferate and are highly resistant to developing HCC in response to a Diethylnitrosamine (DEN)/Phenobarbital (PB) liver tumor-induction protocol [9].
• In this study, we used diethylnitrosamine/phenobarbital treatment to induce hepatocellular carcinomas (HCCs) in either WT mice or Arf(-/-)Rosa26-FoxM1b Tg mice, in which forkhead box M1b (FoxM1b) is overexpressed and alternative reading frame (ARF) inhibition of FoxM1 transcriptional activity is eliminated [10].
• This selectively expanding diploid hepatocyte population, which persisted after AAF withdrawal, could represent the AAF-promoted progeny of diethylnitrosamine-altered cells with constitutive nonpolyploidizing growth properties [11].
• Additional diploid proliferation was detected after initiation with diethylnitrosamine followed by promotion with AAF [11].

Chemical compound and disease context of Nitrosodiethylamine

• A similar 30-fold increase in activity relative to control is present in hepatomas, induced by either 2-AAF or diethylnitrosamine, and in fetal hepatocytes [12].
• To allow a study of beta-catenin mutations in hepatocellular carcinomas (HCCs) induced by exogenous and endogenous carcinogens, we induced tumors in male Fischer 344 rats with N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet [13].
• To investigate the kinetics of strongly induced PNEC hyperplasia in an animal model, we exposed hamsters to a combination of hyperoxia (60% O2) and diethylnitrosamine (DEN) for up to 20 weeks [14].
• Similar changes in phosphorylation were noted in hepatomas induced by diethylnitrosamine and 3'-methyl-4-dimethylaminoazobenzene but not in regenerating, fetal, and neonatal livers [15].
• Rates of conversion of 14C-labeled dimethyl-and diethylnitrosamine by rat and hamster tissue slices to 14CO2 and/or into mutagenic reactants were measured using Salmonella typhimurium G-46 r TA 1530 and fortified tissue fractions in vitro [16].

Biological context of Nitrosodiethylamine

• Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation [17].
• During eight successive isologous passages of hepatoma induced in male C3HA mice by N-nitrosodiethylamine, no common features of tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation [18].
• The effects of treatments with diethylnitrosamine (DENA) and hepatitis B virus (HBV) on macaque monkeys were investigated by virus serology and by light and electron microscopy [19].
• The rates of catalysis of four reactions in the reconstituted enzyme system, including the oxygenation of ethanol to give acetaldehyde, the oxidative dealkylation of N-nitrosodiethylamine to give ethylene and acetaldehyde, and the ring hydroxylation of aniline and p-nitrophenol, are the same with the shortened and full-length enzymes [20].
• A major histocompatibility complex-linked locus in the rat critically influences resistance to diethylnitrosamine carcinogenesis [21].

Anatomical context of Nitrosodiethylamine

• The endoskeletal structure of tumor cells with a characteristic cytoplasmic abnormality initiated in rat liver by the in vivo adminisration of the carcinogen diethylnitrosamine was studied in clonal cell lines established and propagated in vitro [22].
• Histopathology of preneoplastic and neoplastic lesions of the esophagus in BUF rats ingesting diethylnitrosamine [4].
• In the trachea, the fetal target organ, bound radioactivity was restricted to the respiratory epithelium, where diethylnitrosamine-induced tracheal tumors arise [23].
• Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice [18].
• Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture [24].

Associations of Nitrosodiethylamine with other chemical compounds

• In male B6C3F1 mice that received either 15 or 45 ppm diethylnitrosamine [(DENA) CAS: 55-18-5] between 6 and 10 weeks of age, subsequent treatment with 500 ppm sodium phenobarbital in the drinking water resulted in the promotion of liver tumors [25].
• In contrast to L-PK activity, the activity of K-type pyruvate kinase (K-PK) was induced by injections of the carcinogen diethylnitrosamine (CAS: 55-18-5) or the hepatotoxin CCl4 (CAS: 56-23-5) or by the feeding of 3'-MeDAB [26].
• Vinylethylnitrosamine (VEN), an alpha-beta unsaturated analogue of diethylnitrosamine (DEN), which may be formed by the enzymic conversion necessary for carcinogenesis, was synthesized and its biologic effect was examined by sc administration to Syrian hamsters [27].
• The effect of treatment with indomethacin on diethylnitrosamine (DENA, CAS:55-18-5; N-nitrosodiethylamine)-induced esophageal tumors was investigated in 128 C57BL mice [28].
• Intact hepatocytes from Aroclor 1254-treated hamsters were more efficient at metabolizing the aromatic amines and DENA, whereas homogenates were more effective with the hydrocarbons [29].

Gene context of Nitrosodiethylamine

• However, histological examination showed that Mgat3-/- livers had significant numbers of basophilic foci, and by 10-12 months after diethylnitrosamine injection, tumors had developed in Mgat3-/- mice [30].
• However, in diethylnitrosamine-treated mice, the chronic FGFR1 activity promoted an incidence of 44% adenomas at 4 months and 38% hepatocellular carcinoma at 8 months [31].
• Finally, we found a significant decrease in tumor incidence, mass, and malignancy in both male and female cyclin G1-null mice after treatment with the potent hepatocarcinogen N-diethylnitrosamine [32].
• To elucidate the role of HGF in hepatocarcinogenesis, diethylnitrosamine (DEN) was administered to HGF transgenic mice [33].
• CYP2A6 activated NDMA, NDEA, NDPA, NDBA, NMPhA, NPYR, NNN and NNK [34].

Analytical, diagnostic and therapeutic context of Nitrosodiethylamine

• The effect of partial hepatectomy (PH) on alteration of liver foci induced by N-nitrosodiethylamine (DENA) was studied in inbred F344 male rats [35].
• Livers of 6- to 7-week-old male C3H/He, CBA, A, and BALB/c mice were examined by electron microscopy for the presence of intracisternal A particles (ICAP) after administration of diethylnitrosamine (DEN) in drinking water [36].
• Autoradiography in fetal golden hamsters treated with tritiated diethylnitrosamine [23].
• After 16 wk of oral diethylnitrosamine treatment there was a greater than 20-fold increase in hepatic androgen receptor concentration in female rats (control group 0.3 +/- 0.07 fmol/mg cytosol protein; test group 8.36 +/- 0.96 fmol/mg cytosol protein; p less than 0.001, unpaired Student's t-test) [37].
• Rats received weekly intraperitoneal injections of diethylnitrosamine (DEN) followed by a 2-week wash-out period that caused cirrhosis in 14 weeks and multifocal HCC in 18 weeks [38].

References