The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurium. Metabolites were formed by incubation of 5-methylchrysene with the 9000 from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into 9 peaks, A to I. Each peak was collected and tested for mutagenicity with activation. Significant mutagenic activity was observed primarily in peak E and to a lesser extent in peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene and 5-hydroxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.
1,2- & 7,8-Dihydrodiols were the major metabolites of 5-methylchrysene, 7 small amounts of the 9,10-dihydrodiol were also formed following incubation of the compound with rat-liver preparations. Other metabolites detected include 1-, 7- & 9-hydroxy-5-methylchrysene & 5-hydroxymethylchrysene.
The metabolic activation in mouse skin of the strong carcinogen, 5-methylchrysene (5-MeC) was compared to that of the inactive compound, 6-nitro-5-methylchrysene (6-NO2-5-MeC). Metabolites of 6-NO2-5-MeC, formed using rat liver homogenates, were identified based on their spectral properties and were used as markers for studies performed in vivo. In mouse epidermis in vivo, the identified metabolites of 6-NO2-5-MeC were trans-1,2-dihydro-1,2-dihydroxy-6-nitro-5-methylchrysene (6-NO2-5-MeC-1,2-diol), the precursor to a bay region dihydrodiol epoxide, trans-9,10-dihydro-9,10-dihydroxy-6-nitro-5-methylchrysene, and 6-nitro-5-hydroxymethylchrysene. The levels of 6-NO2-5-MeC-1,2-diol formed in mouse epidermis from 6-NO2-5-MeC were greater than those of the proximate carcinogen trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene (5-MeC-1,2-diol) formed from 5-MeC. The further metabolism of 6-NO2-5-MeC-1,2-diol was examined in mouse epidermis under conditions similar to those described previously for 5-MeC-1,2-diol. The extents of formation of 1,2,3,4-tetraols from both dihydrodiols were similar. The chromatographic patterns of DNA adducts formed in mouse epidermis from 6-NO2-5-MeC and 5-MeC were qualitatively similar; however, the extent of formation of DNA adducts from 5-MeC was 15-fold greater than from 6-NO2-5-MeC. The reactions between calf thymus DNA and the bay region 1,2-diol-3,4-epoxides of 5-MeC and 6-NO2-5-MeC were compared; the levels of adducts formed from the bay region diol epoxide of 5-MeC were about four times greater than those formed from the bay region diol epoxide of 6-NO2-5-MeC. The results indicate that the relatively low DNA binding in vivo of 6-NO2-5-MeC may be responsible for its apparent lack of tumorigenicity compared to 5-MeC. It is likely that nitro substitution at the 6-position of 5-MeC interferes with the structural requirements of the 1,2-diol-3,4-epoxide which are necessary for specific DNA interactions.
We have investigated the metabolism of chrysene (CHR) and 5-methychyrsene (5-MeCHR) by Shasta rainbow trout (Oncorhyncus mykiss) and Long Evans rat liver microsomes to assess the effect of a non-benzo ring methyl substituent on the reactions involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). Trout as well as rat liver microsomes metabolized both CHR and 5-MeCHR at essentially similar rates, indicating that the methyl substituent does not alter the substrate specificity of the cytochrome P450(s) involved in the metabolism of the two PAHs. Dihydrodiols were the major CHR metabolites formed by both trout and rat liver microsomes, whereas the trout liver microsomes formed a considerably higher proportion of 5-MeCHR phenols compared to diols, indicating that 5-methyl substitution alters the substrate specificity of trout microsomal epoxide hydrolase for 5-MeCHR epoxides. Unlike trout liver microsomes, rat liver microsomes formed a much greater proportion of 5-MeCHR diols compared to 5-MeCHR phenols, suggesting that 5-MeCHR epoxides are better substrates for the microsomal epoxide hydrolase present in rat liver than for the enzyme in trout liver. Both trout and rat liver microsomes are more efficient at attacking the bay-region bond versus the non-bay-region double bond in chrysene. In contrast the reverse is true in the case of 5-MeCHR, indicating that a non-benzo ring methyl substituent alters the regioselectivity of the enzymes involved in the oxidative metabolism of PAHs.
来源:Hazardous Substances Data Bank (HSDB)
代谢
5-甲基屈蔼有已知的人类代谢物，包括5-甲基-1,2-二氢屈蔼-1,2-二醇。
5-methylchrysene has known human metabolites that include 5-Methyl-1,2-dihydrochrysene-1,2-diol.
IDENTIFICATION AND USE: 5-Methylchrysene (5-MeC) is a solid polycyclic aromatic hydrocarbon. There is no commercial production or known use of this compound. Reference samples of certified high purity are available. HUMAN EXPOSURE AND TOXICITY: It is reasonably anticipated to be a human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals. ANIMAL STUDIES: A group of 25 male mice received sc injections of 0.05 mg highly purified5-MeC once every 2 weeks for 20 wk (total dose, 0.5 mg) and were observed for a further 12 weeks. A total of 22/25 mice had 24 fibrosarcomas, with an average latent period of 25 weeks. 5-MeC was found to be a potent lung carcinogen in strain A/J mice, inducing more than 100 tumors/mouse at a concentration of 200 mg/kg. 5-MeC induced both adenomas and DNA adducts in a dose-dependent manner in the lungs of mice. A strong correlation of lung adenoma induction with the time-integrated DNA adduct level values was observed. 5-MeC was a strong tumor initiator on mouse skin. The environmental carcinogen 5-MeC can be activated to mutagenic metabolites by several isozymes of cytochrome P-450. The resulting reactive diol-epoxides can be detoxified via conjugation by glutathione S-transferases.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
15种单独的多环芳烃（PAHs）基于实验动物研究的充分致癌性证据，合理预期为人类致癌物。/5-甲基屈 CAS 3697-24-3/
The 15 individual PAHs are reasonably anticipated to be human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals. /5-Methylchrysene CAS 3697-24-3/
There is sufficient evidence in experimental animals for the carcinogenicity of 5-methylchrysene. OVERALL EVALUATION: 5-Methylchrysene is possibly carcinogenic to humans (Group 2B).
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：5-甲基屈艿
IARC Carcinogenic Agent:5-Methylchrysene
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)
Gold-Catalyzed 6-<i>Exo</i>-<i>Dig</i>Cycloisomerization: A Versatile Approach to Functionalized Phenanthrenes
作者：Chao Shu、Long Li、Cheng-Bin Chen、Hong-Cheng Shen、Long-Wu Ye
DOI：10.1002/asia.201400034
日期：2014.6
A novel gold‐catalyzed 6‐exo‐dig cycloisomerization of o‐propargylbiaryls has been developed that provides ready access to functionalizedphenanthrenes in largely good to excellent yields. Notable features of this method are readily available starting materials, mild reaction conditions, and broad substrate scope.
A new synthesis of polycyclic aromatic hydrocarbons via titanium(IV)-catalyzed aldol-type condensation of silyl enol ethers with 2-arylacetaldehydes
作者：Pasquale Di Raddo、Ronald G. Harvey
DOI：10.1016/s0040-4039(00)80371-8
日期：1988.1
A novel one-pot synthesis of angular polycyclic hydrocarbon ring systems involving Ti(IV)-catalyzed aldol-type condensation of silylenolethers with 2-arylacetaldehydes and cyclization of the adducts is described.
A new abbreviated synthesis of 5-methylchrysene and its 2-hydroxy- and 8-hydroxy derivatives
作者：Subodh Kumar
DOI：10.1016/0040-4039(96)01393-7
日期：1996.8
The Suzuki reaction has been applied to provide a highly abbreviated synthesis of 5-methylchrysene and its 2-hydroxy- and 8-hydroxy derivatives from easily accessible starting materials.
Emission Factors and Importance of PCDD/Fs, PCBs, PCNs, PAHs and PM<sub>10</sub> from the Domestic Burning of Coal and Wood in the U.K.
作者：Robert G. M. Lee、Peter Coleman、Joanne L. Jones、Kevin C. Jones、Rainer Lohmann
DOI：10.1021/es048745i
日期：2005.3.1
fuels. However, their combined emissions from the domestic burning of coal and wood would contribute only a few percent to annual U.K.emission estimates. Emissions of PAHs and PM10 were major contributors to U.K. national emission inventories. Major emissions were found from the domestic burning for Cl1,2,3DFs, while the contribution of PCDD/F-sigmaTEQ to total U.K.emissions was minor.
本文介绍了当煤和木材经过受控燃烧实验时针对一系列持久性有机污染物（POPs）得出的排放因子（EFs），旨在模拟空间供暖的家庭燃烧。排放了各种各样的持久性有机污染物，煤炭的排放量高于木材的排放量。对于颗粒物，PM10（大约10 g / kg燃料）和多环芳烃（对于sigmaPAHs大约100 mg / kg燃料）获得了最高的EF。对于氯化物，多氯联苯（PCB）的EF最高，而多氯萘（PCN），二苯并-对-二恶英（PCDD）和二苯并呋喃（PCDF）的丰度较低。对于sigmaPCB，EF大约为1000 ng / kg燃料，对于sigmaPCNs大约为100s ng / kg燃料，对于sigmaPCDD / Fs大约为100 ng / kg燃料。该研究证实，一氯化至三氯化二苯并呋喃Cl1,2,3DFs是低温燃烧过程（如煤炭和木材的国内燃烧）的有力指标。结论是，在固体燃料燃烧期间通常形成许多PCB和PC
Substituent Effects and Charge Delocalization Mode in Chrysenium, Benzo[<i>c</i>]phenanthrenium, and Benzo[<i>g</i>]chrysenium Cations: A Stable Ion and Electrophilic Substitution Study
作者：Kenneth K. Laali、Takao Okazaki、Subodh Kumar、Sergio E. Galembeck
DOI：10.1021/jo001268b
日期：2001.2.1
disubstituted chrysenes Ch (5- methyl- 3, 2-methoxy- 19, 2-methoxy-11-methyl- 20, 2-methoxy-5-methyl- 21, and 9-methyl-4H-cyclopenta[def]chrysene 22), monosubstituted benzo[c]phenanthrenes BcPh (3-methoxy- 23, 3-hydroxy- 24), and monosubstituted benzo[g]chrysenes BgCh (12-methoxy- 25; 12-hydroxy- 26) were generated in FSO3H/SO2ClF or FSO3H-SbF5 (4:1)/SO2ClF and studied by low-temperature NMR at 500 MHz. The methoxy
