... It has been reported that nitroreduction, the most important pathway of nitroarene toxification, occurs mainly in the liver and intestine. ... Red cells also possess the metabolic competence to reduce nitroarenes. In particular, 1,8-dinitropyrene, the nitroarene chosen as model compound, was reduced to the corresponding mono- and diamino-derivatives, 1-amino-8-nitropyrene and 1,8-diaminopyrene, by human lysate supplemented with cofactors.
Dinitropyrenes are contaminants in diesel emissions that are mutagenic in bacteria and mammalian cells, and tumorigenic in laboratory animals. In this project, ... the factors that contributed to the extreme genotoxicity of dinitropyrenes in bacteria /were investigated/ and ... if these factors were important in mammalian cells /was determined/. Xanthine oxidase, a mammalian nitroreductase, catalyzed the conversion of the dinitropyrenes to DNA-bound products, but the level of binding did not exceed that observed with 1-nitropyrene. This suggested that factors in addition to nitroreduction were important in the metabolic activation of dinitropyrenes. 1-Nitro-6-nitrosopyrene and 1-nitro-8-nitrosopyrene were synthesized and reacted with DNA under reducing conditions. The same C8-substituted deoxyguanosine adducts were formed that were found in the xanthine oxidase-catalyzed reactions, which confirmed that incubation with this nitroreductase generated reactive N-hydroxy arylamine intermediates. In incubations with rat and human liver microsomes and cytosol, 1-nitropyrene and 1,3-dinitropyrene were reduced to a lesser extent than 1,6- and 1,8-dinitropyrene, which was in accord with their relative mutagenicities. Each of the cytosolic incubations were similar in that oxygen decreased aminopyrene, but not nitrosopyrene, formation. The data indicated that reduced derivatives of the nitrosopyrenes were redox cycling with oxygen, which decreased cytosolic aminopyrene formation. In cytosolic incubations, oxygen inhibited the reduction of 1-nitropyrene and 1,3-dinitropyrene to a greater extent than 1,6- and 1,8-dinitropyrene. By comparison, in microsomal investigations, the nitroreduction of each nitrated pyrene was equally oxygen-sensitive. This apparently was caused by the initial nitroanion radicals reacting with oxygen to decrease nitrosopyrene formation. Although more extensive nitroreduction of each compound was detected in anaerobic incubations, aerobic reduction of these compounds did occur and may be important during in vivo exposure to nitrated pyrenes. When rat liver cytosol was incubated with the nitrated pyrenes, very low levels of DNA binding were detected. Addition of acetyl coenzyme A (AcCoA) to these incubations increased the binding of the dinitropyrenes 20- to 40-fold, while the binding of 1-nitropyrene was not affected. The extent of AcCoA-dependent binding of the dinitropyrenes reflected the amount of nitroreduction; however, the increase in binding did not occur with dog liver cytosol, which was known to be deficient in N-acetylases. These results indicated that cytosolic nitroreductases catalyzed the formation of N-hydroxy arylamine intermediates, which in the case of dinitropyrenes were converted to reactive N-acetoxy arylamines by cytosolic AcCoA-dependent acetylases.
... The ability of rabbit lung to metabolize 1,8-dinitro(4,5,9,10-3H)pyrene by both oxygen-dependent and oxygen-independent pathways has been investigated. Using lung 9000 g supernatant, the biotransformation of 1,8-dinitropyrene to stable metabolites was more extensive in the absence of oxygen. A major proportion of the metabolites was ether-extractable. Five metabolite peaks (A-E) were detected by HPLC in the absence of oxygen. Formation of metabolites A, C, D and E was decreased under aerobic conditions. Metabolites B and C co-chromatographed with the reference standards 1,8-diaminopyrene and 1-acetyl-amino-8-nitropyrene, respectively. The formation of metabolites A and C was dependent on the presence of acetyl coenzyme A. Binding of radiolabel to calf thymus DNA occurred under both anaerobic and aerobic conditions, although there was significantly higher binding in the presence of oxygen. Omission of acetyl coenzyme A significantly increased DNA binding. In experiments where calf thymus DNA was omitted from the incubation medium, covalent binding of radiolabel to acid-precipitable lung S9 macromolecules was detected only under aerobic conditions (11.1 +/- 4.3 pmol/mg protein). The results indicate that rabbit lung can metabolize 1,8-dinitropyrene by both reductive and oxidative pathways. Reductive metabolism is the major pathway for formation of stable metabolites while alkylation of cellular macromolecules occurs primarily via oxidation. There was no correlation between acetyl coenzyme A-dependent acetylation and activation of 1,8-dinitropyrene to reactive species which bind to DNA.
The metabolic activation of dinitropyrenes occurs by reduction of one nitro group to yield N-hydroxy-1-amino-x-nitropyrene, where x is 3, 6 or 8, depending on the original compound. These N-hydroxyarylamine intermediates can undergo acid-catalyzed DNA binding or, in contrast to 1-nitropyrene, which is only N-acetylated, can be converted into highly reactive O-acetyl metabolites by bacterial and mammalian transacetylases. This activation pathway has been shown to be responsible for their extreme mutagenicity in Salmonella. In rat liver cytosolic incubations, 1-nitropyrene and 1,3-dinitropyrene were reduced to a much lesser extent than 1,6- or 1,8-dinitropyrene, which suggests that there may be fundamental differences in the reduction pathways between these nitroPAHs. /Dinitropyrenes/
来源:Hazardous Substances Data Bank (HSDB)
代谢
1,8-二硝基芘已知的人类代谢物包括1-氨基-8-硝基芘。
1,8-dinitropyrene has known human metabolites that include 1-amino-8-nitropyrene.
There is sufficient evidence for the carcinogenicity in experimental animals of 1,8-dinitropyrene. No data were available from studies in humans on the carcinogenicity of 1,8-dinitropyrene. Overall evaluation: 1,8-Dinitropyrene is possibly carcinogenic to humans (Group 2B).
1,8-Dinitropyrene is reasonably anticipated to be a human carcinogen based on sufficient evidence of malignant tumor formation in multiple species of experimental animals, at multiple sites, and by multiple routes of exposure.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：1,8-二硝基芘
IARC Carcinogenic Agent:1,8-Dinitropyrene
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌
IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans
来源:International Agency for Research on Cancer (IARC)
IARC Monographs:Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)
Volume 46: (1989) Diesel and Gasoline Engine Exhausts and Some Nitroarenes
Volume 105: (2013) Diesel and Gasoline Engine Exhausts and Some Nitroarenes
来源:International Agency for Research on Cancer (IARC)
The disposition of ... 1,8-dinitropyrene (DNP) in female BALB/c mice was investigated. In the first 48 hr after oral administration of 1,8-dinitro[4,5,9,10-14C)pyrene ((14C)DNP), 42% of the dose was eliminated in the feces and 12% in the urine. Feces was the major pathway of excretion with 45% of the dose being eliminated by this route in 9 days. Distribution of DNP in various tissues (blood, liver, spleen, lungs, kidneys, stomach, small and large intestine) was studied over 9 days. There was a linear increase in the concentration of radioactive material in the blood, liver and kidneys up to 6 hr after (14)CDNP administration, representing 0.27, 2.9 and 0.21% of the radioactive dose, respectively. The corresponding figures after 24 hr decreased to 0.1, 1.6 and 0.12%, respectively. In comparison, radioactivity present in the spleen and lungs was low and did not significantly change with time. In studies with ligated sections of the gastrointestinal tract, DNP absorption was from the small and large intestine and there was none from the stomach. The rate of absorption of DNP from the small intestine was greater than that from the large intestine, although overall uptake of the compound was poor (more than 80% of the original dose was recovered from the ligated small intestine after 120 min). The data from these studies suggest that although absorption of orally administered DNP is slow, the compound or its metabolites persist in the body for long periods and the liver should be considered as the major target organ.
Diaminopyrene modified reduced graphene oxide as a novel electrode material for excellent performance supercapacitors
作者：Hongwei Kang、Chengpeng Zhang、Yonggui Xu、Weiyang Zhang、Jianhua Jiao、Zhikun Li、LeiLei Zhu、Xiaoqian Liu
DOI：10.1039/c9ra10429a
日期：——
Schematic illustration of the facile synthesis process of DAPrGOs nanocomposites, Ragone plots and the superior cyclic stability of the assembled DAPrGO1//DAPrGO1 SSS.
Chemical Oxidation of Nitrated Polycyclic Aromatic Hydrocarbons: Hydroxylation with Superoxide Anion Radical
作者：Kiyoshi Fukuhara、Naoki Miyata
DOI：10.1021/tx00043a003
日期：1995.1
Nitrated polycyclic aromatic hydrocarbon (nitroPAH) is a potent mutagen which is reductively and/or oxidatively metabolized. Biological oxidation of nitroPAH, such as hydroxylation and epoxidation, is known, but chemicaloxidation has been reported in only a few papers. NitroPAH is barely oxidized by various chemical oxidants because of the electron deficient property of the aromatic ring with the nitro
Role of Human Aldo–Keto Reductases in the Nitroreduction of 1-Nitropyrene and 1,8-Dinitropyrene
作者：Anthony L. Su、Clementina A. Mesaros、Jacek Krzeminski、Karam El-Bayoumy、Trevor M. Penning
DOI：10.1021/acs.chemrestox.2c00271
日期：2022.12.19
the three isoforms, AKR1C1 had the highest catalytic efficiency (kcat/Km) for 1-AP formation, whereas AKR1C3 had the highest catalytic efficiency for 1,8-ANP formation. Use of ultra-performance liquid chromatography high-resolution mass spectrometry verified amine product identity and provided evidence for the formation of nitroso- and hydroxylamino-intermediates in our reactions. Our study expands the
Photosensitive material especially photosensitive presensitized printing plate and leuco-dyes contained therein
申请人：KONICA CORPORATION
公开号：EP0035262A2
公开（公告）日：1981-09-09
A photosensitive material having a photosensitive layer provided on a support which photosensitive layer comprises a compound represented by the formula [i]:
wherein [COUP] represent a 4-equivatent coupler from which a hydrogen is removed at a coupling position thereof,
B is a hydroxy group or
wherein R6 and R7 are individually and alkyl group or they may form a 1-piperidino, 1-piperazino, 1-pyrolidino or 4-morpholino group together with each other,
R1 is an alkyl, aryl, alkylamino or arylamino group, and
R2, R3, R4 and R5 individually are a hydrogen or halogen atom or aliphatic or aromatic group, or R2 and R3 may be fused to form a naphthalene ring.
The invention also relates to a presensitized printing plate as such material and to leuco-dyes contained therein.
Strahlungsempfindliches Beschichtungsmittel und seine Verwendung
申请人：CIBA-GEIGY AG
公开号：EP0092524A2
公开（公告）日：1983-10-26
Polyimide, die aliphatische Gruppen enthalten, sind mit chromophoren aromatischen Polyaziden strahlungsvernetzbar. Lösungen in organischen Lösungsmitteln können als strahlungsempfindliche Beschichtungsmittel zur Herstellung von Isolier- und Schutzlacken und als Photoresists mit hoher thermischer, mechanischer und chemischer Beständigkeit verwendet werden.
