8-Methylbenz[a]anthracene (8-MeBaA) transdihydrodiol metabolites were isolated by reversed-phase and normal-phase HPLCs from incubations of 8-MeBaA with liver microsomes or a reconstituted system containing purified cytochrome P-448 and epoxide hydrolase. Regardless of the enzyme source, the metabolically formed 8-MeBaA trans-3,4- and -5,6-dihydrodiols were found to be enriched in one enantiomeric isomer and differed only in the degree of optical purity. The 8-MeBaA trans-8,9-dihydrodiol formed by liver microsomes from either untreated or phenobarbital-treated rats was enriched with the (+)-enantiomer. In contrast, the 8-MeBaA trans-8,9-dihydrodiol formed either by liver microsomes from 3-methylcholanthrene-treated rats or by the reconstituted rat liver enzyme system containing cytochrome P-448 and epoxide hydrolase was enriched with the (-)enantiomer. These results indicate that, in catalyzing the formation of 3,4- and 5,6-epoxide intermediates, the interaction with the unsubstituted 3,4- and 5,6-double bonds of 8-MeBaA by the different forms of cytochrome P-450 occur preferentially on the same face of the aromatic plane and they differ only in the degree of stereoselectivity. However, different forms of cytochrome P-450 may interact with different faces of the aromatic plane at the methyl-substituted 8,9-double bond of 8-MeBaA, resulting in the formation of trans-8,9-dihydrodiols enriched in different enantiomeric forms. This demonstrates that different forms of cytochrome P-450 may catalyze the epoxidation reaction preferentially at different sides of the methyl-substituted double bond of a planar polycyclic hydrocarbon molecule. These properties may be used to further classify and to understand the enzyme-substrate interactions of the different forms of cytochrome P-450 in the drug-metabolizing enzyme systems.
Metabolism of the carcinogen 8-hydroxymethylbenz[a]anthracene (8-HOCH2-BA) with liver microsomes from 3-methylcholanthrene-treated rats resulted in 12 identifiable metabolites. Trans-1,2-, 3,4-5,6-, 8,9-, and 10,11-dihydrodiols are among the identified metabolites. The major enantiomers of the trans-dihydrodiols have 1R,2R, 3R,4R, 5R,6R, 8S,9S, and 10R,11R absolute configurations, respectively. Metabolites formed by liver microsomes from untreated as well as 3-methylcholanthrene-, phenobarbital-, and polychlorinated biphenyl-treated immature male Sprague-Dawley rats were quantified by using specifically tritium-labeled [3H-CH2]8-HOCH2-BA as the substrate. The identification of an 8,9-dihydrodiol as a metabolite of 8-HOCH2-BA indicates that a hydroxymethyl substituent does not prevent the enzymatic oxidation at the hydroxymethyl-substituted 8,9-double bond of 8-HOCH2-BA. ...
IDENTIFICATION AND USE: 8-Methylbenz(a)anthracene (8-MBA) is a solid. It can be formed from incomplete combustion of organic materials. It is used mostly in biochemical research. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: The tumor-initiating activity of the 3,4-dihydrodiols (diols) as well as other metabolites of 8-MBA and 8-hydroxymethylbenz[a]anthracene (8-OHMBA) were examined in the classical 2-stage initiation-promotion model on mouse skin. These data indicate that the 3,4-diol of 8-MBA is a good candidate as a proximate carcinogen of 8-MBA and further suggest that the bay region 3,4-diol-1,2-epoxide is a likely ultimate carcinogen of this compound on mouse skin. in the classical two-stage initiation-promotion experiment, 8-MBA was causing 1.0 papillomas/mouse. In other experiment, mice were administered 8-MBA sc at a dose of 3 mg in the first month and 5 mg at 3 and 9 months. 5.5 lung tumors were present per mouse at the 7-month observation time. However, 8-MCA did not produce transformed animal cells in culture. There appeared to be little quantitative correspondence between carcinogenic and mutagenic potency for this group of chemicals.
Immediate First Aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/
Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary. ... For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 L of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatics hydrocarbons and related compounds/
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The specificity of in-vitro transformation of normal embryonic cells exposed to carcinogenic hydrocarbons was investigated in hamsters and mice. Golden-hamster or SWR-mice embryos were minced and cell suspensions inoculated onto irradiated dishes containing rat embryo feeder layers. Cells for cloning were seeded for 7 to 10 days. Cultures were examined microscopically. Compounds tested were applied on cell cultures by millipore disc filters or by colloidal suspension in growth medium. Transformed cultures were trypsinized and inoculated subcutaneously into adult animals. Tumors were palpated during development, then removed and examined histologically. The transformed cells displayed a hereditary random pattern of growth, ability to grow continuously, and were resistant to benz(a)pyrene (50328) (BP) when tested in culture. Transformed cells in culture were obtained with 3-methylcholanthrene (56495) (MCA), 7,12-dimethylbenzo(a)anthracene (57976) and 10-methylbenz(a)anthracene (2381159), in-vivo, but not with 8-methylbenz(a)anthracene (2381319), chrysene (218019), and pyrene (129000). Carcinogenic hydrocarbons induced direct transformation of normal cells to tumor cells in-vitro. Fibroblasts and epithelial type cells were found with high frequency during transformation in culture. BP induced 25.6 percent transformation of clones, 1 to 2 days after addition of the carcinogen. BP and MCA produced transformed cells, which were not found in cultures of untreated controls. After long periods in culture both untreated and treated mouse cells grew progressively as tumors after inoculation into adult SWR-mice. The authors conclude that expression of transformation is dependent on cell division.
A Pd(II)-catalyzed cascade synthesis of diverse polycyclicaromatichydrocarbons via transient directing group strategy has been developed, involving the consecutive arylation, cyclization and aromatization. The efficiency and practicality were demonstrated by wide substrate range, concise synthetic pathway and mild reaction conditions. The subsequent transformations of the benz[a]anthracene core accessed
已经开发了一种通过Pd（II）催化的通过瞬态导向基团策略级联的多种多环芳烃，涉及连续的芳基化，环化和芳构化。广泛的底物范围，简明的合成途径和温和的反应条件证明了其效率和实用性。苯并[ a ]蒽核心的后续转化获得了天然的生物活性PAH分子。
Phenanthrene Derivatives. IX. 1-Alkyl-1-hydroxytetrahydrophenanthrenes and Related Compounds
作者：W. E. Bachmann、A. L. Wilds
DOI：10.1021/ja01270a038
日期：1938.3
Coördination of Polycyclic Aromatic Hydrocarbons with Silver Ion; Correlation of Equilibrium Constants with Relative Carcinogenic Potencies<sup>1</sup>
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