Disease relevance of N-Dinitrosopiperazine

• Carcinogen-induced DNA amplification in vitro: overreplication of the simian virus 40 origin region in extracts from carcinogen-treated CO60 cells [1].
• The preneoplastic lesions were hyperplastic alveolar nodules (HAN) derived originally from mice treated by hormonal stimulation (D2), exposed to a chemical carcinogen (C4), or spontaneously expressing mouse mammary tumor virus (CV2) and maintained by serial transplantation [2].
• NEPHGE 57 was dramatically increased in C4 and CV2 tissues and cultured cells and may be related to expression of squamous metaplasia and keratinization which are characteristic of these lesions [2].
• METHODS.: Normal and tumorigenic ovarian surface epithelial cells were isolated as described by Roby and coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawpik O, Persons DL, Smith PG, Terranova PF, Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogen 2000;21 (4):585. [1]] [3].
• Two nitrosamides (N-methyl-N'-nitro-N-nitrosoguanidine and methylnitrosourea) and three nitrosamines (dimethylnitrosamine, nitrosomorpholine, and dinitrosopiperazine) and their deuterium-containing analogs were tested for reversion of a nonsense mutation in the tyr locus of Escherichia coli WU 3610 (tyr-, leu-) [4].

High impact information on N-Dinitrosopiperazine

• New knowledge in the field of carcinogenesis is developing, and modifications of the Environmental Protection Agency's "Interim Guideline for Carcinogen Risk Assessment" must be made periodically [5].
• Sequential changes in tumor development induced by 1,4-dinitrosopiperazine in the nasal cavity of F344 rats [6].
• (Abu-Zeid,M., Nagata, K., Miyata,M., Ozawa,S., Fukuhara,M. and Yamazoe,Y., 1991, An arylamine acetyltransferase (AT-1) from Syrian golden hamster liver: cloning, complete nucleotide sequence, and expression in mammalian cells. Mol. Carcinogen., 4, 81-88) [7].
• A recent hypothesis proposes that aberrant gene expression during tumorigenesis may occur through conversion of inactive response elements with high homology to hormone response elements into functional enhancers by carcinogen-induced point mutations at critical positions (Nawaz et al., Mol. Carcinogen., 7, 76-82, 1993) [8].
• Long-term feeding study in C17 mice administered saccharin coated betel nut and 1,4-dinitrosopiperazine in combination [9].

Biological context of N-Dinitrosopiperazine

• The recent National Institute of Environmental Health Sciences/National Toxicology Program Carcinogen Prediction Challenge elicited a valuable array of predictions of the carcinogenicity of chemicals tested in the lifetime rodent bioassay [10].
• The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays [11].
• The Missense Genetic Polymorphisms of Human CYP2A13: Functional Significance in Carcinogen Activation and Identification of A Null Allelic Variant [12].
• Isoform 1 consisted of 2,700 bp, from which a 667 amino acid sequence was deduced and found to be identical with that of OS-9 cDNA from osteosarcoma cells [Su et al. (1996) Mol. Carcinogen. 15, 270-275] [13].
• In a previous study, we demonstrated point mutations in codons 12 and 61 of Ha-ras gene among eleven transitional cell carcinomas (TCC), one undifferentiated carcinoma, and two sarcomas of the urinary bladder (Mol Carcinogen 3:210-215, 1990) [14].

Anatomical context of N-Dinitrosopiperazine

• Likewise, a Mr 46,000 polypeptide (IEF 46), which has been tentatively identified previously as a keratin, was absent in normal epithelium but present in all abnormal tissues except the C4 and CV2 HAN [2].
• Metabolites of the Carcinogen 2-Amino-alpha-carboline Formed in Male Sprague-Dawley Rats in Vivo and in Rat Hepatocyte and Human HepG2 Cell Incubates [15].
• Determination of N-mononitrosopiperazine and N,N'-dinitrosopiperazine in human urine, gastric juice and blood [16].
• Ten DNP-treated animals survived the treatment; six had tumors related to the treatment, nasal mucosa adenocarcinomas or neuroblastomas in five and a transitional cell carcinoma of the bladder in one [17].
• RI also inhibited precancerous and cancerous lesions in the nasal cavity and nasopharynx and oesophagus of rats induced by dinitrosopiperazine [18].

Associations of N-Dinitrosopiperazine with other chemical compounds

• The diet of saccharin coated betel nut failed to potentiate the carcinogenicity of 1,4-dinitrosopiperazine [9].
• Anhydrous piperazine and a drug formulation were found to have a content of 0.2 to 20 micrograms of the suspected carcinogen N-mononitrosopiperazine per gram piperazine, but no detectable amounts of the carcinogen N,N'-dinitrosopiperazine [19].
• An expert panel was convened to evaluate the U.S. Environmental Protection Agency's "Proposed Guidelines for Carcinogen Risk Assessment" through their application to data sets for chloroform (CHCl3) and dichloroacetic acid (DCA) [20].
• Within the framework of EPA's Proposed Guidelines for Carcinogen Risk Assessment, it is proposed that the most appropriate cancer risk descriptor for aldrin/dieldrin, relating to the mouse liver tumor response, is 'not likely a human carcinogen', a descriptor consistent with the example of phenobarbital cited by EPA [21].

Gene context of N-Dinitrosopiperazine

• Chemical carcinogens. A review and analysis of the literature of selected chemicals and the establishment of the Gene-Tox Carcinogen Data Base. A report of the U.S. Environmental Protection Agency Gene-Tox Program [22].
• N,N'-Dinitrosopiperazine (DNPZ) can induce nasopharyngeal carcinoma in rats and increased sister chromatid exchange frequency in human embryonic nasopharyngeal epithelial (HENE) cells [23].
• An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 13--Applying the EPA Proposed Guidelines for Carcinogen Risk Assessment to a set of asbestos lung cancer mortality data [24].
• Effect of N,N'-dinitrosopiperazine on in vitro expression of human cytochrome P450 2E1 [25].

Analytical, diagnostic and therapeutic context of N-Dinitrosopiperazine

• The most comprehensive example is EPA's recent draft final Guidelines for Carcinogen Risk Assessment. In all programs, however, the principal role of mechanistic information has been to support the positive results observed in epidemiological studies or to discount the relevance of positive results observed in experimental animal bioassays [26].
• A rapid, selective and sensitive method for the determination of N-mononitrosopiperazine and N,N'-dinitrosopiperazine in human urine, gastric juice and blood has been developed using gas-liquid chromatography with thermal energy analysis [16].
• A simple and specific reversed phase HPLC method for the determination of dinitrosopiperazine in simulated gastric juice using UV detection was reported [27].
• Pesticide chemicals (more than 40) with limited evidence for carcinogenicity in animal experiments, and assigned to Group C according to the EPA Guidelines for Carcinogen Risk Assessment, were further analyzed and ranked by refining the weight of the evidence evaluation [28].

References