Disease relevance of DPN

• 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 [1].
• Mutagenic activities of oxidized derivatives of N-nitrosodipropylamine in the liver cell-mediated and Salmonella typhimurium assays [2].
• Application of 2,2'-dihydroxydi-n-propylnitrosamine, another postulated intermediate of di-n-propylnitrosamine, led to development of various types of pancreatic duct adenomas and ductal carcinomas in high percentages of hamsters [3].
• Praziquantel (250 mg/kg body weight, i.p.) was given 4, 12 or 20 weeks after infection of DHPN-treated animals (two 1000 mg/kg i.p. injections at weeks 0 and 2) with 60 OV metacercariae (at week 4) [4].
• The findings thus indicate that enhancement of DHPN-initiated bile duct carcinogenesis by opisthorchiasis is both rapid and to a large degree irreversible [4].

High impact information on DPN

• N-Nitroso-2,6-dimethylmorpholine (DMNM) was examined in Syrian golden hamsters in a comparative study of N-N-dipropylnitrosamine (DPN) metabolites [5].
• Because DMDPN failed to induce neoplasms in other organs, the carcinogenicity of DPN or its beta metabolites for the lungs, liver, pancreas, and kidneys was not explained by this experiment [6].
• Cytochrome P450 1A1 exhibited no activity for metabolism of NDPA, NDBA and NBPA [7].
• Pretreatment of rats with PB caused a 10-fold increase in the sensitivity of hepatocytes to the cytotoxic actions of NDPA, NBPA and NDBA as measured by trypan blue exclusion, whereas PYR pretreatment increased the sensitivity of hepatocytes to NDPA and NBPA, but not to NDBA [8].
• Microsomes from PYR-pretreated rats exhibited increased activities for formation of formaldehyde and propionaldehyde from NDPA and NBPA [7].

Biological context of DPN

• N-Nitrosodi-n-propylamine induces organ specific mutagenesis with specific expression times in lacZ transgenic mice [9].
• Mechanism of alkylation by N-nitroso compounds: detection of rearranged alcohol in the microsomal metabolism of N-nitrosodi-n-propylamine and base-catalyzed decomposition of N-n-propyl-N-nitrosourea [10].
• One tenth of the LD50 as a single dose of various N-nitroso compounds (N-nitrosodimethylamine; NDMA, N-nitrosodiethylamine; NDEA, N-nitrosoethylpropylamine; NEPA, N-nitrosodipropylamine; NDPA, N-nitrosomethylethylamine; NMEA, N-nitroso-methylbutylamine; NMBA and N-nitrosoethylbutylamine; NEBA) was administrated into male mice [11].
• The present results regarding changed enzyme phenotype in lung lesions suggest important similarities at the biochemical level for the process of neoplasia in the different target organs of DHPN in the hamster and indicate that GST-P may be a useful 'marker' for lung neoplasia [12].
• CL in the cytochrome P-450 enzyme system remained unchanged during the biotransformation of carcinogens such as diethylnitrosamine, dipropylnitrosamine and benzo(a)pyrene as compared with the control [13].

Anatomical context of DPN

• That nitrosodipropylamine is metabolized at the alpha-position by liver microsomes from Fischer-344 rats supports the widely held contention that such metabolism is responsible for the carcinogenicity of nitrosamines [14].
• Comparative study on the carcinogenicity of N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopyrrolidine and N-nitrosodi-n-propylamine to the lung of Syrian golden hamsters following intermittent instillations to the trachea [15].
• The higher level of nitrosodipropylamine led to death of all the animals with carcinomas of the liver, nasal cavity and esophagus by the 40th week [16].
• The metabolites of DPN induced additional tumors in the digestive tract [17].
• Treatment with both substances additionally resulted in vascular neoplasms of the liver, while DPN only caused tumors in the pharynx, esophagus and forestomach [18].

Associations of DPN with other chemical compounds

• Carcinogenesis in Fischer rats by nitrosodipropylamine, nitrosodibutylamine and nitrosobis(2-oxopropyl)amine given by gavage [16].
• Metabolism of N-nitrosodi-n-propylamine and N-nitrosodiallylamine by isolated rat hepatocytes [19].
• Determination of N-nitrosodipropylamine in trifluralin emulsifiable concentrates using minicolumn cleanup and gas chromatography with thermal energy analyzer [20].
• After subcutaneous administration of dipropylnitrosamine (DPN) to Syrian hamsters, gas-liquid chromatographic analysis of the 16-h urine revealed the DPN metabolites, 2-hydroxypropyl-, 2-oxopropyl-, and methylpropylnitrosamines [17].

Gene context of DPN

• These new recombinant strains exhibit a four- to five-fold greater mutagenic response to dimethylnitrosamine, diethylnitrosamine, and dipropylnitrosamine than strains that contain only CYP2E1 and reductase, and are over 100-fold more sensitive to nitrosamines than the parental strains in the presence of an exogenous activating system (S9 fraction) [21].
• In microsomes from PYR-pretreated rats inhibition by mAbs also showed a role for cytochrome P450 2E1 in depropylation of NDPA [7].

References