Summary: A potent epoxide hydrase and aryl hydrocarbon hydroxylase inhibitor. It enhances the tumor-initiating ability of certain carcinogens.

Top Publications

  1. Giri A. Genetic toxicology of propylene oxide and trichloropropylene oxide--a review. Mutat Res. 1992;277:1-9 pubmed
    ..In this review an attempt has been made to evaluate and update the genotoxic effects of propylene oxide and trichloropropylene oxide based on the available literature. ..
  2. Shi X, Yu S. Trichloropropane and dichlorohydrin associated with painful peripheral neurotoxicity. J Clin Neurosci. 2013;20:1387-9 pubmed publisher
    ..However, the pathogenesis remains unidentified. TCP may be added to the list of industrial products that are toxic to the peripheral sensory nerves. ..
  3. Moghaddam M, Motoba K, Borhan B, Pinot F, Hammock B. Novel metabolic pathways for linoleic and arachidonic acid metabolism. Biochim Biophys Acta. 1996;1290:327-39 pubmed
    ..This manuscript is the first report of techniques for the separation and identification of regio and geometrical isomer of an interesting class of oxylipins and their metabolism by liver microsomes and S-9 fractions to THF-diols. ..
  4. Walters J, Combes R. Activation of benzo[a]pyrene and aflatoxin B1 to mutagenic chemical species by microsomal preparations from rat liver and small intestine in relation to microsomal epoxide hydrolase. Mutagenesis. 1986;1:45-8 pubmed
    ..However, TCPO strongly inhibited microsomal epoxide hydrolase activity and activation of BP and AFB due to liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  5. Marshall A, Caldwell J. Influence of modulators of epoxide metabolism on the cytotoxicity of trans-anethole in freshly isolated rat hepatocytes. Food Chem Toxicol. 1992;30:467-73 pubmed
    ..These data are discussed in terms of the role of anethole epoxide in the cytotoxicity of trans-anethole. ..
  6. Zhao S, Zhao E, Shen P, Zhao M, Sun J. An atom-efficient and practical synthesis of new pyridinium ionic liquids and application in Morita-Baylis-Hillman reaction. Ultrason Sonochem. 2008;15:955-9 pubmed publisher
    ..Furthermore, the application of new ionic liquids were tested as solvents in Morita-Baylis-Hillman reaction, in some cases, good results were obtained. ..
  7. Einistö P, Hooberman B, Sinsheimer J. Base-pair mutations caused by six aliphatic epoxides in Salmonella typhimurium TA100, TA104, TA4001, and TA4006. Environ Mol Mutagen. 1993;21:253-7 pubmed
    ..In addition, since the reproducibility of the effect of the triazole on TA104 reversions was poor, TA-->AT transversions were not eliminated as also contributing to the mutagenicity of these epoxides in this Salmonella strain. ..
  8. Das L, Das S, Chu E, Sinsheimer J. Chromosomal aberrations in mouse lymphocytes exposed in vivo and in vitro to aliphatic epoxides. Mutat Res. 1993;299:19-24 pubmed
    ..The difference in the order of genotoxicity for the two test systems can be explained on the basis of a much shorter half-life for TCPO than for the other epoxides. ..
  9. Cameron H, Waller P, Ramsay L. Drug treatment of intermittent claudication: a critical analysis of the methods and findings of published clinical trials, 1965-1985. Br J Clin Pharmacol. 1988;26:569-76 pubmed
    ..In view of the deficiencies in previous trials, we propose guidelines for future studies with regard to trial design, sample-size and methods of exercise testing. ..

More Information


  1. Wells P, Wilson B, Lubek B. In vivo murine studies on the biochemical mechanism of naphthalene cataractogenesis. Toxicol Appl Pharmacol. 1989;99:466-73 pubmed
  2. Luo G, Qato M, Guenthner T. Hydrolysis of the 2',3'-allylic epoxides of allylbenzene, estragole, eugenol, and safrole by both microsomal and cytosolic epoxide hydrolases. Drug Metab Dispos. 1992;20:440-5 pubmed
    ..The susceptibilities of these epoxides to rapid hydrolysis by both epoxide hydrolases may explain their low genotoxic potencies in vivo. ..
  3. Yoshizawa H, Uchimaru R, Ito T, Tashiro F, Ueno Y. Nuclear envelope-dependent binding of aflatoxin B1 to DNA. J Environ Pathol Toxicol Oncol. 1990;10:79-88 pubmed
  4. Paulini H, Schimmer O. Mutagenicity testing of rutacridone epoxide and rutacridone, alkaloids in Ruta graveolens L., using the Salmonella/microsome assay. Mutagenesis. 1989;4:45-50 pubmed
    ..Evidence is presented that rutacridone is metabolized by rat liver enzymes to the corresponding epoxide as the ultimate mutagen. ..
  5. Pace Asciak C, Laneuville O, Su W, Corey E, Gurevich N, Wu P, et al. A glutathione conjugate of hepoxilin A3: formation and action in the rat central nervous system. Proc Natl Acad Sci U S A. 1990;87:3037-41 pubmed
    ..These findings suggest that these products in the hepoxilin pathway of arachidonic acid metabolism formed by the rat brain may function as neuromodulators. ..
  6. Lovern M, Maris M, Schlosser P. Use of a mathematical model of rodent in vitro benzene metabolism to predict human in vitro metabolism data. Carcinogenesis. 1999;20:1511-20 pubmed
    ..The model should be useful in quantifying human risk due to benzene exposure and explicitly accounts for interindividual variation in CYP2E1 activity. ..
  7. Sahali Sahly Y, Balani S, Lin J, Baillie T. In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4. Chem Res Toxicol. 1996;9:1007-12 pubmed
    ..One or more of these electrophilic species may be responsible for the autocatalytic destruction of cytochrome P450 enzymes which accompanies L-754,394 metabolism in vitro and in vivo. ..
  8. Wierckx F, Wedzinga R, Timmers Reker A, Beland F, Meerman J, Mulder G. DNA adduct formation in liver following the administration of [3H]2-nitrofluorene to rats in vivo. Carcinogenesis. 1991;12:2053-8 pubmed
    ..In vitro experiments with inhibitors of the enzyme epoxide hydrolase indicated that epoxidation of 2-NF may play a role in the microsomal bioactivation of this compound...
  9. Liu X, Qiu Z, Shen W, Peng X. [The clinical analysis of 18 cases with acute trichloropropane poisoning]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012;30:307-9 pubmed
    ..Liver injury in those 18 cases was not obvious. Lymphocyte micronucleus of peripheral blood were found in all 18 cases. ..
  10. Den Besten P, Lemaire P, Livingstone D. NADPH-, NADH- and cumene hydroperoxide-dependent metabolism of benzo[a]pyrene by pyloric caeca microsomes of the sea star Asterias rubens L. (Echinodermata: Asteroidea). Xenobiotica. 1994;24:989-1001 pubmed
    ..7. Incubations of pyloric caeca microsomes with BaP and a superoxide anion radical-generating system (xanthine/xanthine oxidase) produced putative protein adducts but no free metabolites. ..
  11. Ye Y, Scharping C, Holder G. The hepatic metabolism of two carcinogenic dimethylbenz[c]acridines in control and induced rats: the distribution and the mutagenicity of metabolites. Carcinogenesis. 1995;16:787-93 pubmed
    ..The activation of these two dimethylbenz[c]acridines to mutagens appears to be through bay-region diolepoxides following patterns seen in other aza-aromatic compounds and the polycyclic aromatic hydrocarbons. ..
  12. Kawabata T, White K. Benzo(a)pyrene metabolism by murine spleen microsomes. Cancer Res. 1989;49:5816-22 pubmed
  13. Reed G, Layton M, Ryan M. Metabolic activation of cyclopenteno[c,d]pyrene by peroxyl radicals. Carcinogenesis. 1988;9:2291-5 pubmed
    ..These findings expand the range of potentially toxic substrates to be considered for activation by peroxyl radical pathways. ..
  14. Wilson A, Tingle M, Kelly M, Park B. Evaluation of the generation of genotoxic and cytotoxic metabolites of benzo[a]pyrene, aflatoxin B1, naphthalene and tamoxifen using human liver microsomes and human lymphocytes. Hum Exp Toxicol. 1995;14:507-15 pubmed
    ..This indicates that both intracellular and extracellular bioactivation of these two compounds can produce genotoxicity. In contrast, naphthalene and tamoxifen were non-genotoxic. ..
  15. Gadberry M, Denicola D, Carlson G. Pneumotoxicity and hepatotoxicity of styrene and styrene oxide. J Toxicol Environ Health. 1996;48:273-94 pubmed
    ..These results demonstrated the greater role of epoxide hydrolase in styrene oxide detoxification. ..
  16. Davis C, Pirmohamed M, Kitteringham N, Allott R, Smith D, Park B. Kinetic parameters of lymphocyte microsomal epoxide hydrolase in carbamazepine hypersensitive patients. Assessment by radiometric HPLC. Biochem Pharmacol. 1995;50:1361-6 pubmed
    ..This did not affect the kinetic parameters of lymphocyte microsomal epoxide hydrolase. Our results suggest that there is normal HYL1 activity in lymphocytes of hypersensitive patients using cis-stilbene oxide as a substrate. ..
  17. Shi K, Zhang X, Zhang J. [Experimental study of xenogeneic heart valve material]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2003;17:496-500 pubmed
  18. Platt K, Petrovic P, Seidel A, Beermann D, Oesch F. Microsomal metabolism of picene. Chem Biol Interact. 1988;66:157-75 pubmed
    ..The lacking carcinogenicity of picene could therefore result from the inability of microsomal enzymes to transform its M-region dihydrodiol to dihydrodiol bay-region epoxides in amounts necessary to initiate carcinogenesis. ..
  19. Shou M, Gonzalez F, Gelboin H. Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase. Biochemistry. 1996;35:15807-13 pubmed
    ..Our results provide a clear understanding of how these enzymes catalyze overall stereoselective metabolism at the K-region of the PAHs. ..
  20. Morel J, Neerchal N. Clustered binary logistic regression in teratology data using a finite mixture distribution. Stat Med. 1997;16:2843-53 pubmed
    ..In a simulation study we investigate the type I error rate and the power of the maximum likelihood ratio test when the data follow a finite mixture distribution. ..
  21. Thornton Manning J, Chou M, Fu P, Heflich R. Microsomal activation of 1- and 3-nitrobenzo[a]pyrene to mutagens in Chinese hamster ovary cells. Mutagenesis. 1988;3:233-7 pubmed
    ..g. bay-region diol epoxides; (ii) reactive nitroarene oxides may contribute to mutation induction by 3-nitro-BaP; and (iii) metabolic routes involving trans-9,10-dihydrodiol formation result in detoxification. ..
  22. Hartsfield J, Holmes L, Morel J. Phenytoin embryopathy: effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL/6J mice. Biochem Mol Med. 1995;56:131-43 pubmed
    ..This suggests either that differences in the genotypes of Swiss and C57BL/6J mice may be a contributing factor or that other teratogenic mechanisms were involved. ..
  23. Glatt H, Wameling C, Elsberg S, Thomas H, Marquardt H, Hewer A, et al. Genotoxicity characteristics of reverse diol-epoxides of chrysene. Carcinogenesis. 1993;14:11-9 pubmed
    ..Unlike other investigated diastereomeric pairs of diol-epoxides, it was also shorter-lived than its syn-diastereomer (t1/2 = 340 min). ..
  24. Tingle M, Pirmohamed M, Templeton E, Wilson A, Madden S, Kitteringham N, et al. An investigation of the formation of cytotoxic, genotoxic, protein-reactive and stable metabolites from naphthalene by human liver microsomes. Biochem Pharmacol. 1993;46:1529-38 pubmed
    ..This is rapidly detoxified by microsomal epoxide hydrolase, the efficiency of which can be readily determined by measurement of the ratio of the stable metabolites, naphthalene 1,2-dihydrodiol and 1-naphthol. ..
  25. Fifer E, Howard P, Heflich R, Beland F. Synthesis and mutagenicity of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide, microsomal metabolites of 1-nitropyrene. Mutagenesis. 1986;1:433-8 pubmed
    ..Since 1-nitropyrene is metabolized by oxidative pathways in vivo, these K-region oxides may contribute to the toxicities elicited by this compound. ..