Administration of the antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) in the diet caused a marked increase in the specific activity of epoxide hydratase (EC 4.2.1.63) in hepatic microsomes of CD-1 mice. The increases in epoxide hydratase activities produced by BHA were far greater (11-fold) than were those produced by the administration of well-known enzyme inducers such as 3-methylcholanthr...

Administrationof the antioxidant 2(3)-tert-butyl-4-hy droxyanisole(BHA)in the diet causeda markedincrease in the specific activity of epoxide hydratase (EC 4.2.1.63) in hepatic microsomesof CD-i mice. The increases in epoxide hydratase activities produced by BHA were far greater (11-fold)than were those producedby the admin istrationof well-knownenzymeinducerssuchas 3-meth ylcholanthrene,phenob...

The structural features of polycyclic polyether natural products can, in some cases, be traced to their biosynthetic origin. However in case that are less well understood, only biosynthetic pathways that feature dramatic, yet speculative, epoxide-opening cascades are proposed. We summarize how such epoxide-opening cascade reactions have been used in the synthesis of polycyclic polyethers (see s...

Epoxide hydrolase and glutathione S-transferase activities toward trans- and cis-stilbene oxides were measured in 3 strains of Drosophila melanogaster. Differences in age dependence, substrate selectivity and subcellular location were detected suggesting the presence of multiple forms of these enzymes. In addition, interstrain differences indicate the presence of genetic variation for epoxide h...

The major mutational hot spots in human cancers occur at CpG sequences in the p53 gene. It is generally presumed that the majority of mutations at these sites result from the endogenous deamination of methylated cytosine. Using a UvrABC incision method, we have found that cytosine methylation greatly enhances guanine alkylation at all CpG sites in the p53 gene by a variety of carcinogens, inclu...

The distribution of rat liver epoxide hydrolase in various subcellular fractions was investigated by immuno-electron-microscopy. Ferritin-linked monospecific anti-(epoxide hydrolase) immunoglobulins bound specifically to the cytoplasmic surfaces of total microsomal preparations and smooth and rough microsomal fractions as well as the nuclear envelope. Specific binding was not observed when the ...

Simultaneous monitoring of carbamazepine and its metabolities is helpful in providing information on the induction process via the epoxide-diol route. The present method involves the liquid-chromatographic analysis of 1.0 mL of plasma for carbamazepine at concentrations of 0.025 to 4.0 mg/L and for both the 10,11-epoxide and 10,11-transdiol metabolites at concentrations of 0.01 to 1.0 mg/L. Wei...

Polycyclic aromatic hydrocarbons (PAHs) are significant environmental pollutants representing an important risk factor in human cancers. DNA adducts formed by the ultimate carcinogens of PAHs are potentially toxic, mutagenic and carcinogenic. DNA repair represents an important defense system against these genotoxic insults. Using a human cell-free system we have examined repair of DNA lesions i...

Hepatic Microsomal Epoxidation of Bromobenzene to Phenols and Its Toxicological Implication. LAU, S. S. AND ZANNONI, V. G. (1979). Toxicol. Appl. Pharmacol. 50, 309318. In vitro microsomal hepatic epoxidation of bromobenzene in rats and mice is presented in this study. Formation of o-bromophenol via bromobenzene-2,3-epoxide and p-bromophenol via bromobenzene-3,4-epoxide was assayed enzymaticall...

The pioneering work of Gerry Brooks on cyclodiene insecticides led to the discovery of a class of enzymes known as epoxide hydrolases. The results from four decades of work confirm Brooks' first observations that the microsomal epoxide hydrolase is important in foreign compound metabolism. Brooks and associates went on to be the first to carry out a systematic study of the inhibition of this en...