Dibenz[a,h]anthracene   中文名称: 1,2:5,6-二苯并蒽

Absorption, Distribution and Excretion
Upon topical application /1 uM/mouse/ to mouse skin, dibenz(a,h)anthracene became bound to DNA in skin at treated area to the extent of 15 pmol/mg DNA. This cmpd showed a max level of binding 72 hr after treatment, compared with 19-24 hr for other polycyclic hydrocarbons similarly tested.
In study reported as abstract, it was suggested that DB(a,h)A or its metabolites cross the placenta.
Dietary absorption efficiencies and elimination rates of acenaphthylene, 1-phenyl naphthalene, 2-methyl anthracene, 9-methyl anthracene, triphenylene, perylene, benzo[b]fluorene, dibenzo[a,h]anthracene, benzo [ghi]perylene and coronene were examined in rainbow trout. Subadult fish were exposed to 10 mg of each chemical over 5 days and polycyclic aromatic hydrocarbon (PAH) levels were monitored during the following 25 days. The results indicated that PAHs were not accumulated by trout through dietary exposure because of the combined effects of poor absorption efficiencies and rapid elimination rates. ...

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Metabolism / Metabolites
Yields 1,2-dihydro-1,2-dihydroxydibenzanthracene, 3,4-dihydro-3,4-dihydroxydibenzanthracene, 5,6-dihydro-5,6-dihydroxydibenzanthracene, and S-(5,6-dihydro-6-hydroxydibenzanthr-5-yl)glutathione in rats. /From table/
Yields dibenzanthracene-7,14-quinone in mice. /From table/
Yields dibenzanthracene-5,6-oxide in rats. /From table/
Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for dibenz[a,h]anthracene. Dibenz[a,h]anthracene has a "bay-region" structure. It is metabolized by mixed-function oxidases to dihydrodiols that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice.
For more Metabolism/Metabolites (Complete) data for Dibenz(a,h)anthracene (13 total), please visit the HSDB record page.
Dibenzo(a,h)anthracene has known human metabolites that include dibenzo(a,h)anthracene 1,2-epoxide and dibenzo(a,h)anthracene 3,4-epoxide.
PAH metabolism occurs in all tissues, usually by cytochrome P-450 and its associated enzymes. PAHs are metabolized into reactive intermediates, which include epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations. The phenols, quinones, and dihydrodiols can all be conjugated to glucuronides and sulfate esters; the quinones also form glutathione conjugates. (L10)

Toxicity Summary
IDENTIFICATION AND USE: Dibenz(a,h)anthracene (DBA) forms white crystals or a pale yellow solid. It is used as a research chemical. HUMAN EXPOSURE AND TOXICITY: DBA is a probable human carcinogen. Neuroblastoma risk in a child was increased with higher maternal exposure to DBA. ANIMAL STUDIES: Addition of DBA to food for a total dose of 9-19 mg over a period of 5-7 months in mice led to the appearance of tumors of the forestomach in 7/22 survivors after 1 year; 1 of these tumors was a carcinoma. In a later experiment, 20 back-cross mice receiving 0.4 mg DBA per day orally developed 2 squamous cell carcinomas and 11 papillomas of the forestomach within 406 days. In a similar experiment tumors were produced in the lung, heart, and intestine. Squamous carcinomas of forestomach were induced if emulsion was stabilized against the breaking effect of gastric juices. No tumors were seen among 10 Syrian golden hamsters receiving 20 applications of 0.2% solutions DBA over a period of 10 weeks, 5 of which were alive at 50 weeks. DBA was positive in differential survival assays using DNA-repair-proficient/-deficient strains of bacteria and was mutagenic to Salmonella typhimurium with metabolic activation. In cultured mammalian cells DBA was mutagenic and induced unscheduled DNA synthesis with metabolic activation. It was positive in assays for morphological transformation. In the one available study, it induced sister chromatid exchange but not chromosomal aberrations in vivo. Carcinogenic polycyclic aromatic hydrocarbons can produce an immunosuppressive effect. This was first observed in administration of high doses of 3-methylcholanthrene and DBA to mice. DBA has a "bay-region" structure. It is metabolized by mixed-function oxidases to dihydrodiols that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice. The influence of near-ultraviolet light (UVA) on the DBA cytotoxicity and genotoxicity in larvae of the amphibian Pleurodeles waltl was evaluated and DBA was not found to be clastogenic. ECOTOXICITY STUDIES: Of 121 pigeons which received intramuscular injections of 3 mg DBA were observed for 13 months, 14 developed fibrosarcoma at the injection site. No tumors were found among 32 untreated controls. Intramuscular injection of 0.4% DBA in lard induced sarcomas in 15/31 fowl within 45 months. Injection of 0.3-0.5 mg DBA in olive oil into the kidney of frogs (Rana pipiens) produced renal adenocarcinomas in 26% of survivors compared with 3% of controls.
The ability of PAH's to bind to blood proteins such as albumin allows them to be transported throughout the body. Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. The main carcinogenic metabolite of benzo(a)pyrene is the diol-epoxide trans-9,10-epoxy-7,8-dihydrodiol. (L10, L23, A27, A32)

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Interactions
... The influence of near-ultraviolet light (UVA) on the cytotoxicity and genotoxicity of 7 polycyclic aromatic hydrocarbons (PAH) in larvae of the amphibian Pleurodeles waltl /was evaluated/. Benz[a]anthracene (BA), 7,12-benz[a]anthraquinone (BAQ) and anthracene (Ac) proved to be lethal at low doses (some ppb), and the following order of genotoxicity was observed: BA approximately BAQ > DMBA > DMA (9,10-dimethylanthracene). Ac, AQ (9,10-anthraquinone) and DBA (dibenz[a,h]anthracene) were not found to be clastogenic. In the larvae reared in normal conditions (subdued natural daylight/darkness alternation) or in continuous darkness, the BA derivatives were shown to be more genotoxic than BA itself: DMBA > BAQ > BA; BA (>/= 187.5 ppb) slightly increased the level of micronuclei in circulating erythrocytes, while DMBA was strongly clastogenic, in line with their reported carcinogenicity. In other experiments, rearing media alone (i.e., water containing BA, BAQ or DMBA) were UVA-irradiated for 24 hr, and then tested on larvae in the dark ('IR-UV/dark' conditions). Photodegradation of BA (50 and 100 ppb) gave rise to clastogenic products. By contrast, DMBA (12.5, 25 or 50 ppb) was destroyed by UVA, and we suggested that any potentially mutagenic photoproducts formed were not in sufficient amounts to yield a positive response in the newt micronucleus test.
Carcinogenicity of hydrocarbon mixt predominantly found in automobile exhaust gas condensate was attributed to the syncarcinogenic action of benzo[a]pyrene, dibenz[a,h]anthracene, benz[a]anthracene, and benzo[b]fluoranthene. The 4 carcinogenic hydrocarbons were tested in mice with single dosage levels of 4-12 ug ... It was not possible to demonstrate an inhibitory action of most of the weak-to-inactive hydrocarbons; on the contrary, an additive effect of the two types could be observed. At very high doses (almost 10 times higher than the highest doses selected in the rest of the trial) the group of substances which were supposed to be non-carcinogenic also proved to be biologically effective.
The genotoxicity of 15 polycyclic aromatic hydrocarbons was determined with the alkaline version of the comet assay employing V79 lung fibroblasts of the Chinese hamster as target cells. These cells lack the enzymes necessary to convert PAHs to DNA-binding metabolites. ... 11 PAHs, i.e., benzo[a]pyrene (BaP), benz[a]anthracene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, fluoranthene, anthanthrene, 11H-benzo[b]fluorene, dibenz[a,h]anthracene, pyrene, benzo[ghi]perylene and benzo[e]pyrene caused DNA strand breaks even without external metabolic activation, while naphthalene, anthracene, phenanthrene and naphthacene were inactive. When the comet assay was performed in the dark or when yellow fluorescent lamps were used for illumination the DNA-damaging effect of the 11 PAHs disappeared. White fluorescent lamps exhibit emission maxima at 334.1, 365.0, 404.7, and 435.8 nm representing spectral lines of mercury. In the case of yellow fluorescent lamps these emissions were absent. Obviously, under standard laboratory illumination many PAHs are photo-activated, resulting in DNA-damaging species. This feature of PAHs should be taken into account when these compounds are employed for the initiation of skin cancer. ...

[1]. Stereoselective metabolism of dibenz(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens. Environ Health Perspect. 1990 Aug:88:37-41.

[2]. Hepatic genotoxicity and toxicogenomic responses in Muta™Mouse males treated with dibenz[a,h]anthracene. Mutagenesis. 2013 Sep;28(5):543-54.

Dibenz[a,h]anthracene can cause cancer according to an independent committee of scientific and health experts.
Dibenz[a,h]anthracene appears as white crystals or pale yellow solid. Sublimes. (NTP, 1992)
Dibenz[a,h]anthracene is an ortho-fused polycyclic arene. It has a role as a mutagen.
Dibenzo[a,h]anthracene is a crystalline, carcinogenic aromatic hydrocarbon consisting of five fused benzene rings, produced by the incomplete combustion of organic matter. Dibenzo(a,h)anthracene is primarily found in gasoline exhaust, tobacco smoke, coal tar, soot and certain food products, especially smoked and barbecued foods. This substance is used only for research purposes to induce tumorigenesis. Dibenzo(a,h)anthracene is a mutagen and is reasonably anticipated to be a human carcinogen.
Dibenzo(a,h)anthracene is one of over 100 different polycyclic aromatic hydrocarbons (PAHs). PAHs are chemicals that are formed during the incomplete burning organic substances, such as fossil fuels. They are usually found as a mixture containing two or more of these compounds. It is one ingredient of cigarette. (L10)

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Mechanism of Action
Several of the biological effects of PAHs, such as enzyme induction of xenobiotic metabolizing enzymes, immunosuppression, teratogenicity and carcinogenicity, are thought to be mediated by activation of the aryl hydrocarbon receptor. This receptor is widely distributed and has been detected in most cells and tissues. There is also evidence that the aryl hydrocarbon receptor acts through a variety of pathways and, more recently, that cross-talk with other nuclear receptors enables cell type-specific and tissue-specific control of gene expression. Translocation of the activated aryl hydrocarbon receptor to the nucleus may require threshold concentrations of the ligand. Various oxidative and electrophilic PAH metabolites are also known to induce enzyme systems via anti-oxidant receptor elements. The biological effects of aryl hydrocarbon receptor and anti-oxidant receptor element signalling involve a variety of cellular responses, including regulation of phase I and II metabolism, lipid peroxidation, production of arachidonic acid-reactive metabolites, decreased levels of serum thyroxine and vitamin A and persistent activation of the thyroid hormone receptor. Aryl hydrocarbon receptor signalling may result in adaptive and toxic responses or perturbations of endogenous pathways. Furthermore, metabolic activation of PAHs produces cellular stress. This in turn activates mitogen mediated protein kinase pathways, notably of Nrf2. The Nrf2 protein dimerizes with Maf oncoproteins to enable binding to an anti-oxidant/electrophilic response element, which has been identified in many phase I/II and other cellular defense enzymes and controls their expression. Therefore, cellular stress may be regulated independently of aryl hydrocarbon receptor-mediated xenobiotic metabolizing enzymes. /Polycyclic aromatic hydrocarbons/
The current understanding of the carcinogenesis of polycyclic aromatic hydrocarbons (PAHs) in experimental animals is almost solely based on two complementary mechanisms: those of the diol epoxide and the radical cation. Each provides a different explanation for the data observed in experimental animals. The diol epoxide mechanism features a sequence of metabolic transformations of PAHs, each of which leads to potentially reactive genotoxic forms. In general, PAHs are converted to oxides and dihydrodiols, which are in turn oxidized to diol epoxides. Both oxides and diol epoxides are ultimate DNA-reactive metabolites. PAH oxides can form stable DNA adducts and diol epoxides can form stable and depurinating adducts with DNA through electrophilic carbonium ions. The inherent reactivities of oxides and diol epoxides are dependent on topology (e.g. bay regions, fjord regions, cyclopenta rings), and the reactivity of diol epoxides is further dependent on factors such as stereochemistry and degree of planarity. Both stable and depurinating adducts are formed primarily with guanines and adenines, and induce mutations (e.g. in ras proto-oncogenes) that are strongly associated with the tumorigenic process. Some mutagenic PAH diols, oxides and diol epoxides are tumorigenic in experimental animals. One-electron oxidation creates radical cations at a specific position on some PAHs. The ease of formation and relative stabilities of radical cations are related to the ionization potential of the PAH. Additional important factors in the radical cation mechanism are localization of charge in the PAH radical cation and optimal geometric configuration, particularly the presence of an angular ring. The radical cation mechanism results in the formation of depurinating DNA adducts with guanines and adenines, which generate apurinic sites that can induce mutations in ras proto-oncogenes, which are strongly associated with tumorigenesis. /Polycyclic aromatic hydrocarbons/

C22H14

278.35

278.109

53-70-3

5889

White to off-white solid powder

1.2±0.1 g/cm3

524.7±17.0 °C at 760 mmHg

262-265 °C(lit.)

264.5±15.1 °C

0.0±0.7 mmHg at 25°C

1.812

7.14

0

0

0

0

22

361

0

LHRCREOYAASXPZ-UHFFFAOYSA-N

InChI=1S/C22H14/c1-3-7-19-15(5-1)9-11-17-14-22-18(13-21(17)19)12-10-16-6-2-4-8-20(16)22/h1-14H

naphtho[1,2-b]phenanthrene

AI3-18996; DB(a,h)A; Dibenz[a,h]anthracene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。