... Both the in vitro metabolism of (3H)6-Nitrochrysene (NC) by 9000 g supernatants (S9) prepared from the livers of preweanling mice and the in vivo metabolism of (3H)NC in these animals. The in vitro covalent binding of primary metabolites of NC to DNA after further reductive and/or oxidative metabolism was then examined in an attempt to define the metabolic activation pathway responsible for the formation of carcinogen--DNA adducts in NC-treated preweanling mice. NC-1,2-dihydrodiol, NC-9,10-dihydrodiol, 6-aminochrysene (AC), and several unidentified compounds were found in ethyl acetate extracts of incubations containing (3H)NC and liver S9 from 1- or 8-day-old BLU:Ha mice. Comparison of the in vivo metabolism of NC in 1-day-old animals and 8-day-old animals which had been treated with NC on day 1 indicated that the formation of AC and the two NC dihydrodiols was greater in the younger animals. Further metabolism of NC-1,2-dihydrodiol by S9 from 8-day-old mice yielded AC-1,2-dihydrodiol as a major product. Incubation of AC-1,2-dihydrodiol, calf thymus DNA and liver microsomes from 3-methylcholanthrene-induced rats yielded a single major adduct that was chromatographically and chemically identical to the major adduct formed in (3H)NC- and (3H)-AC-treated preweanling mice. The results indicated that the major DNA adduct found in vivo is derived from the further metabolism of the proximate carcinogen AC-1,2-dihydrodiol.
... The major metabolic activation pathway of 6-nitrochrysene in newborn mice is initially through the formation of the proximate tumorigen trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene with subsequent formation of 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-aminochrysene ... The ability of human hepatic and pulmonary microsomes to metabolize 6-nitrochrysene was investigated. The major metabolites identified in 11 hepatic microsomes were trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene, trans-9,10-dihydro-9,10-dihydroxy-6-nitrochrysene, trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene, 6-aminochrysene, and chrysene-5,6-quinone. Following the incubations of 6-nitrochrysene with 11 different human pulmonary microsomes, qualitatively similar metabolic patterns were obtained, although quantitative differences were evident. These results demonstrated that human liver and lung are capable of metabolizing 6-nitrochrysene to known potent carcinogenic metabolites via ring oxidation and nitroreduction. In an attempt to define the roles of individual human hepatic P450 involved in the metabolism of 6-nitrochrysene, the catalytic activities known to be associated with a specific P450 were analyzed and compared with the levels of each metabolite of 6-nitrochrysene formed with the same microsomes. Rates of phenacetin O-deethylation (P450 1A2) and nifedipine oxidation (P450 3A4) were well correlated with the rates of formation of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6-aminochrysene, respectively. Inhibition studies with specific P450 inhibitors and antibodies further support the view that P450 1A2 and P450 3A4 are the major forms responsible for the formation of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6-aminochrysene, respectively, in human liver. Further metabolism of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene appears to require P450 3A4. In the human lung, P450 1A1 appears to play a major role in the metabolism of 6-nitrochrysene to trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene ...
... Three female CD rats were injected ip with [3,4,9,10-3H]6-nitrochrysene (6-NC) [9 umol/rat (346 uCi/rat)], and urine and feces were collected daily for 3 days. In the first 24 hr, radioactivity corresponding to 1.3% of the dose was excreted in the urine, whereas 23.0% was recovered in the feces. After 3 days, the total excretions in urine and feces were 2.8% and 34.9% of the dose, respectively. Radioactivity measured in various organs 3 days after injection of [3,4,9,10-3H]6-NC amounted to 24.8% of the administered dose. Fecal metabolites were identified, based on comparison of their chromatographic characteristics with those of standards, as trans-1,2-dihydro-1,2-dihydroxy-6-NC, chrysene-5,6-quinone, and 6-aminochrysene (6-AC); the structure of the latter was further confirmed by mass spectrometry and UV spectral analysis. Metabolites identified in the urine were 6-AC, trans-1,2-dihydro-1,2-dihydroxy-6-NC, and trans-9,10-dihydro-9,10-dihydroxy-6-NC in free forms and also as glucuronide and/or sulfate conjugates. The (32)P-postlabeling assay was used to determine the metabolic pathways that were leading to DNA adduct formation in the target (colon) and nontarget (liver, lung, and mammary tissues) organs of female CD rats injected with 6-NC under conditions identical to those of the bioassay (total, 14.8 umol/rat; single ip injections on days 1, 8, 15, 22 and 29). Twenty-four hr after the last carcinogen administration, the levels of the adduct derived from trans-1,2-dihydro-1,2-dihydroxy-6-AC were higher than those derived from N-hydroxy-6-AC in all organs examined; however, the highest levels of DNA adducts were found in the lung and not in the target organ, the colon. Although the role of each adduct in colon carcinogenesis needs to be determined, the results favor the ring oxidation and nitroreduction combination pathway as the primary contributor to the activation of 6-NC as a colon carcinogen in the rat.
The environmental pollutant 6-nitrochrysene (6-NC) is a potent mammary carcinogen in the rat. To determine if the results obtained in 6-NC-treated rodents can be applicable to humans, ... its metabolic activation in primary cultures of human breast cells prepared from tissues obtained from reduction mammoplasty from 3 women and in a cultured, immortalized human mammary epithelial cell line (MCF-10A), as well as estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-435s) human breast cancer cell lines /was examined/. Metabolites identified following 24 hr incubations of (3H)6-NC (2.5, 5.0 and 10 uM) with human breast cells were derived from ring-oxidation (trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene [1,2-DHD-6-NC]) and nitro-reduction (6-aminochrysene [6-AC]); chrysene-5,6-quinone (C-5,6-Q) was also detected. Levels of metabolites (pmol/mg protein) varied greatly depending on the concentration of 6-NC and the individual breast tissue used; 1,2-DHD-6-NC, ranged from not detected to 15.6 +/- 1.0; 6-AC, from 11.5 +/- 4.0 to 155 +/- 10.2; C-5,6-Q, from 18.3 +/- 10.8 to 196.7 +/- 15.4. Qualitatively similar metabolic profiles were obtained upon incubation of [(3)H]6-NC with MCF-10A, MCF-7 and MDA-MB-435s. ... 1,2-dihydroxy-6-aminochrysene (1,2-DH-6-AC ranged from not detected to 50.4 +/- 9.8). Some of the metabolites identified in our study are known to be proximate carcinogenic forms of 6-NC in rodents. MCF-7 was the most efficient cell line in catalyzing 6-NC to genotoxic metabolites, and ... the major DNA adduct is chromatographically identical to that found in the mammary gland of rats treated by gavage with 6-NC and that obtained from the incubation of [(3)H]1,2-DHD-6-NC with MCF7 cells or from nitro-reduction of 1,2-DHD-6-NC in the presence of 2'-deoxyguanosine 5'-monophosphate in vitro. This is the first report to demonstrate the ability of human breast cells, MCF-10A, and breast cancer cell lines to activate 6-NC to metabolites that can damage DNA.
来源:Hazardous Substances Data Bank (HSDB)
代谢
6-硝基屈萘已知的代谢物包括1,2-DHD-6-NC和N-羟基-6-AC。
6-nitrochrysene has known human metabolites that include 1,2-DHD-6-NC and N-hydroxy-6-AC.
There is sufficient evidence for the carcinogenicity in experimental animals of 6-nitrochrysene. No data were available from studies in humans on the carcinogenicity of 6-nitrochrysene. Overall evaluation: 6-Nitrochrysene is possibly carcinogenic to humans (Group 2B).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
6-硝基屈可以被合理地预期为一种人类致癌物，因为根据多个实验动物物种多个部位的充分致癌性证据。
6-Nitrochrysene is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity at multiple sites in multiple species of experimental animals.
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：6-硝基芘
IARC Carcinogenic Agent:6-Nitrochrysene
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：2A组：可能对人类致癌
IARC Carcinogenic Classes:Group 2A: Probably 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)
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
Nitration of Polycyclic Aromatic Hydrocarbons Using a Supported Catalyst
作者：Amy C. Smith、Lorena D. Narvaez、Bridget G. Akins、Moses M. Langford、Thomas Gary、Victoria J. Geisler、Farooq A. Khan
DOI：10.1080/00397919908085892
日期：1999.12.1
Abstract We report the use of catalyst, sulfuric acid supported on silica-gel, as promising method for facile, high yielding, regioselective syntheses of mononitrated polycyclic aromatic hydrocarbons, 6-nitrochrysene, 1-nitropyrene, 1-nitronaphthalene, 2-nitrofluorene, 3-nitrofluoranthene, and 9-nitroanthracene.
A facile reduction of aromatic nitro compounds to aromatic amines by samarium and iodine
作者：Bimal K. Banik、Chhanda Mukhopadhyay、M.S. Venkatraman、Frederick F. Becker
DOI：10.1016/s0040-4039(98)01555-x
日期：1998.10
A simple method for the reduction of aromaticnitrocompounds to aromaticamines was developed using samarium and catalytic amounts of iodine.
开发了一种使用sa和催化量碘将芳族硝基化合物还原为芳族胺的简单方法。
Indium/Ammonium Chloride Mediated Selective Reduction of Aromatic Nitro Compounds: Practical Synthesis of 6-AminoChrysene
作者：Bimal K. Banik、Michelle Suhendra、Indrani Banik、Frederick F. Becker
DOI：10.1080/00397910008087002
日期：2000.10
Abstract Reduction of aromatic and heteroaromatic nitro compounds to the corresponding amino compounds was achieved by indium/ammonium chloride induced reaction in aqueous ethanol. This method was extended for the preparation of large quantities of 6-aminochrysene in excellent yield.
Inefficient Nucleotide Excision Repair in Human Cell Extracts of the <i>N</i>-(Deoxyguanosin-8-yl)-6-aminochrysene and 5-(Deoxyguanosin-<i>N</i><sup>2</sup>-yl)-6-aminochrysene Adducts Derived from 6-Nitrochrysene
were incubated with NER-competent nuclear extracts from human HeLa cells. The efficiency of repair of these lesions was ∼8 times less efficient than that in the case of the well-known and excellent substrate of NER, the intrastrand cross-linked cis-diaminodichloroplatinum II adduct in double-stranded DNA (cis-Pt), but similar to N2-dG adducts derivedfrom the (+)-bay region diol epoxide of B[a]P [(+)-trans-B[a]P-N2-dG]
普遍存在的环境因素[例如，多核芳烃 (PAHs) 及其硝化衍生物 (NO 2 -PAHs)] 已知会诱发啮齿类动物的乳腺癌，被认为是诱发类似人类癌症的潜在人类危险因素。尽管 6-硝基化合物 (6-NC)在环境中的含量低于其他 NO 2 -PAHs，但它是大鼠体内最强的致癌物质；其致癌性不仅高于致癌的多环芳烃苯并[ a ]芘（B[ a ]P），也高于著名的致癌杂环芳香胺2-氨基-1-甲基-6-苯基咪唑[4,5- b]吡啶（PhIP）。大鼠研究和体外试验表明 6-NC 可以通过简单的硝基还原被激活，导致 6-羟基氨基丁烯 (N-OH-6-AC) 的形成；该代谢物产生N -(deoxyguanosin-8-yl)-6-aminochrysene ( N -[dG-8-yl]-6-AC) 和 5-(deoxyguanosin- N 2 -yl)-6-aminochrysene (5-[ dG- N
