Search PubMed⌕ Search

Biomedical subjects

F Oesch

Publications and source records attributed to F Oesch.

At least 127 records · Page 7Linked to original sources
PubMed1994

Gap junctional intercellular communication of cultured rat liver parenchymal cells is stabilized by epithelial cells and their isolated plasma membranes.

The gap junctional intercellular communication (GJIC) determined by measuring dye coupling with Lucifer yellow, decreased within 3 d from 66% to 28% in monocultures of rat liver parenchymal cells. Coculturing of the parenchymal cells with a nonparenchymal epithelial cell line from rat liver resulted in increased and stabilized intercellular communication (83% after 3 d). The presence of isolated plasma membrane vesicles of the nonparenchymal epithelial cells also stabilized the intercellular communication between the liver parenchymal cells (70% after 3 d). When liver parenchymal cells were cocultured with a rat liver fibroblast cell line the gap junctional communication between the parenchymal cells was not stabilized (43% after 3 d), and isolated plasma membrane vesicles of the fibroblast were also unable to support the GJIC in parenchymal cells (35% after 3 d). It is concluded that plasma membrane constituents of the nonparenchymal epithelial cells were responsible for the stabilization of the GJIC between parenchymal cells. A heterotypic gap junctional communication between parenchymal and nonparenchymal cells was not observed.

Animals↗
PubMed1994

Different enzyme kinetics during the glutathione conjugation of the four stereoisomers of the fjord-region diolepoxides of benzo[c]phenanthrene by the mu-class rat liver glutathione S-transferase HTP II.

The enzyme-catalysed conjugation of each of the four stereoisomers of trans-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (B[c]PhDE) with glutathione (GSH) by HTP II, a novel isolated mu-class GSH transferase from the liver of untreated rat, was studied. All four stereoisomers were substrates for GSH transferase HTP II. The enzymatic reaction shows three different types of enzyme kinetics: substrate inhibition for (-)-anti-B[c]PhDE with (R,S,S,R)-absolute configuration, allosteric behavior using (+)-anti-B[c]PhDE with (S,R,R,S)-absolute configuration and Henri-Michaelis-Menten kinetics with both the (-)-syn- and (+)-syn-enantiomers, with (S,R,S,R)- and (R,S,R,S)-absolute configuration, respectively. When the concentration of these diolepoxides was varied (using 2 mM GSH), the apparent Vmax values were 1975 nmol/min x mg for (-)-anti-B[c]PhDE and about 60 nmol/min x mg for both (-)-syn- and (+)-syn-B[c]PhDE, with the corresponding Km values of 1.05 and 0.20 mM. The reaction of (+)-anti-B[c]PhDE determined by applying the Hill equation had an estimated Vmax value of 930 nmol/min x mg. On varying the concentration of GSH, linear Lineweaver-Burk plots were obtained. No competitive effect could be observed using a mixture of (-)-anti- and (+)-anti-enantiomers, indicating that their binding sites are different and independent. It was also shown, that the binding sites of (+)-anti- and both syn-enantiomers were different and independent of each other, while there was a small effect on the binding of the syn-enantiomers caused by (-)-anti-B[c]PhDE. All products of the reaction between GSH and the dihydrodiol epoxides of benzo[c]phenanthrene could be resolved by HPLC and were identified and quantitated using the corresponding synthetic GSH conjugates.

Animals↗
PubMed1994

Sequence similarity of mammalian epoxide hydrolases to the bacterial haloalkane dehalogenase and other related proteins. Implication for the potential catalytic mechanism of enzymatic epoxide hydrolysis.

Direct comparison of the amino acid sequences of microsomal and soluble epoxide hydrolase superficially indicates that these enzymes are unrelated. Both proteins, however, share significant sequence similarity to a bacterial haloalkane dehalogenase that has earlier been shown to belong to the alpha/beta hydrolase fold family of enzymes. The catalytic mechanism for the dehalogenase has been elucidated in detail [Verschueren et al. (1993) Nature 363, 693-698] and proceeds via an ester intermediate where the substrate is covalently bound to the enzyme. From these observations we conclude (i) that microsomal and soluble epoxide hydrolase are distantly related enzymes that have evolved from a common ancestral protein together with the haloalkane dehalogenase and a variety of other proteins specified in the present paper, (ii) that these enzymes most likely belong to the alpha/beta hydrolase fold family of enzymes and (iii) that the enzymatic epoxide hydrolysis proceeds via a hydroxy ester intermediate, in contrast to the presently favoured base-catalyzed direct attack of the epoxide by an activated water.

Amino Acid Sequence↗
PubMed1994

Glycolaldehyde causes DNA-protein crosslinks: a new aspect of ethylene oxide genotoxicity.

After in vitro incubation of human peripheral mononuclear blood cells with glycolaldehyde (a putative metabolite of ethylene oxide) for 2 h at 37 degrees C, a dose-dependent increase in DNA crosslinks was observed in a dose range between 1 and 10 mM using the alkaline filter elution technique. The elution rate of mononuclear blood cells after treatment with ionizing radiation (600 cGy) was reduced more than 5-fold if cells were incubated with 10 mM glycolaldehyde for 2 h. After treatment with proteinase K DNA crosslinks were no longer detected in cells incubated with glycolaldehyde. Therefore the crosslinks produced by glycolaldehyde could clearly be identified as DNA-protein crosslinks. Additionally glycolaldehyde induced DNA single-strand breaks in a dose range between 1 and 10 mM. The elution rate of mononuclear blood cells was increased about 18-fold if cells were incubated with 5 mM glycolaldehyde for 2 h using an elution procedure with proteinase K. In vitro incubation of mononuclear cells with ethylene oxide for 2 h at 37 degrees resulted in a dose-dependent increase in DNA single-strand breaks between 0.5 and 10 mM ethylene oxide. Moreover, a time-dependent increase in DNA single-strand breaks after incubation with 1.5 mM ethylene oxide was observed with an increased number of single-strand breaks already detectable after 15 min and a maximum level which was detected after 2 h of incubation. However, no DNA-DNA or DNA-protein crosslinks could be detected although a wide concentration range and many different incubation times were tested. Therefore DNA crosslinks, for which evidence was found in mononuclear blood cells of humans occupationally exposed to ethylene oxide, are possibly generated by glycolaldehyde, a putative intermediate in the metabolism of ethylene oxide to glycolic acid.

Acetaldehyde↗
PubMed1994

Deficiency of bile acid transport and synthesis in oval cells from carcinogen-fed rats.

Freshly isolated oval cells, which we obtained from the livers of rats fed a choline-deficient/DL-ethionine-supplemented diet, did not transport bile acids. Compared with freshly isolated rat hepatocytes they took up only negligible amounts of [3H]taurocholate or [14C]cholate. The cells bound small amounts of radioactive bile acids. This portion of the total cell-associated radioactivity was enhanced on membrane permeabilization. In contrast to cultured liver parenchymal cells from untreated rats, no bile acid synthesis was detected in cultured oval cells. Cultured oval cells also lost the ability to conjugate exogenously added cholate (100 mumol/L) with taurine or glycine. However, when liver parenchymal cells were isolated from carcinogen-fed rats, bile acid uptake was diminished compared with that in hepatocytes from control animals. In particular, the maximum values of taurocholate and cholate uptake were decreased by 75% and 50%, respectively, whereas the Michaelis-Menten constant values were not altered. The study demonstrates that (a) oval cells lack typical liver parenchymal cell-specific properties such as bile acid uptake, bile acid synthesis and conjugation of bile acids with taurine/glycine and therefore do not contribute to bile acid dependent bile formation (b) proliferating in livers of rats fed a choline-deficient/DL-ethionine-supplemented diet are part of the bile duct epithelial cell compartment); and (c) bile acid uptake is reduced in liver parenchymal cells of rats fed a choline deficient/DL-ethionine-supplemented diet, and this effect is due to a decrease in transport capacity without a decrease in transport affinity.

Animals↗
PubMed1994

Metabolism and cytotoxicity of aflatoxin B1 in cultured rat hepatocytes and nonparenchymal cells: implications for tumorigenesis.

Liver cells, isolated from male Sprague-Dawley rats and established in primary culture, were treated with a dose of 180 pmol aflatoxin B1 (AFB1) for 2 hr. Reticuloendothelial nonparenchymal cells (NPC) metabolized a total of 28% of the AFB1. In contrast, parenchymal epithelial cells or hepatocytes (HC) were highly efficient in conjugating AFB1 to water-soluble products (50-70% of the dose) but also bound a large proportion (27%) of the toxin to cellular macromolecules. In comparison to NPC, HC bound 90-fold more AFB1 per cell. Cytotoxicity in primary cultures was evaluated by changes in membrane integrity (lactate dehydrogenase release), inhibition of glutathione-S-transferase activity and cell monolayer morphology over a range of AFB1 doses. No response was detected in NPC, whereas HC exhibited dose-related cytotoxic responses to AFB1. In rat liver both cell types form AFB1-DNA adducts in a dose-dependent fashion and yet only epithelial cell carcinomas have been observed in whole animal studies. The possibility that cell-specific AFB1 cytotoxicity produces a promotional stimulus for hepatocellular carcinoma is discussed.

Aflatoxin B1↗
PubMed1994

Oncogene overexpression in non-small-cell lung cancer tissue: prevalence and clinicopathological significance.

In contrast to small-cell lung cancer, few data are available on the role of oncogene overexpression in non-small-cell lung cancers (NSCLC). To determine the prevalence and extent of the transcriptional activation of cancer genes in NSCLC we investigated the level of mRNA of the three important cellular oncogenes--erbB2, Ki-ras, and c-myc--in 39 surgically or endoscopically obtained tumor samples and 24 samples of normal bronchopulmonary tissue taken from the same patients. Tissue RNA was prepared and the specific mRNA analyzed by the highly sensitive nuclease S1 protection assay. Oncogene mRNA in the tumors was quantified by comparison with the homogeneously weak signals in normal lung tissue preparations with densitometry. The presence of two- to four-fold excess RNA was defined as moderate and a greater than fourfold RNA amount as strong gene overexpression. In contrast to normal tissue the oncogene mRNA amount varied considerably among tumors, showing increases up to 64-fold in erbB2, 13-fold in Ki-ras, and 57-fold in c-myc. Moderate and strong (in brackets) mRNA overexpression occurred with 33% (33%) in erbB2, 36% (18%) in Ki-ras, and 18% (23%) in c-myc. Simultaneous overexpression of two genes was observed with 41% and increased mRNA of all genes tested with 20% of the NSCLC samples. Augmented oncogene mRNA was observed most frequently in large-cell carcinoma. The c-myc overexpression was significantly more prevalent in large-cell cancer than in adenocarcinoma. Tumor differentiation was negatively correlated with c-myc mRNA amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Drug-metabolizing enzyme activities in freshly isolated oval cells and in an established oval cell line from carcinogen-fed rats.

The activities of several different phase I and phase II drug-metabolizing enzymes were measured in freshly isolated oval cells from rats fed a choline-deficient/DL-ethionine-supplemented diet for 6 weeks and also in vitro in the established oval cell line OC/CDE 6. No cytochrome P450 was spectrophotometrically measurable in both preparations and two cytochrome P450-dependent monoxygenase activities, aminopyrine N-demethylase and ethoxyresorufin O-deethylase, could not be detected in the oval cells of both sources. However, cytosolic glutathione transferase, microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities were clearly measurable in oval cells. Similar enzyme activities were found in freshly isolated and cultured oval cells. The highest activities of these three enzymes were detected during the exponential growth phase of the cultured cells; thereafter the activities decreased until the cells reached confluency. Changes in phenol UDP-glucuronosyltransferase (UGT1A1) mRNA levels paralleled the variations in UDP-glucuronosyltransferase activity, i.e. they were high in exponentially growing oval cells and low in confluent cell cultures. Taking into account that oval cells are able to proliferate in the livers of rats continuously fed a choline-deficient/DL-ethionine-supplemented diet and that none of the analyzed drug metabolizing enzymes are involved in the activation or detoxication of DL-ethionine, the described pattern might be part of a more general, nonspecific, protection mechanism enabling these cells to overcome the cytotoxic effects of a variety of carcinogens and to proliferate even in their presence. Furthermore, the expression of microsomal epoxide hydrolase, cytosolic glutathione transferase and UDP-glucuronosyltransferase appears to depend on the proliferative status of the cells.

Animals↗
PubMed1994

Genotoxic risk for humans due to work place exposure to ethylene oxide: remarkable individual differences in susceptibility.

Single strand breaks of DNA of peripheral mononuclear blood cells from 97 male and female workers occupationally exposed to ethylene oxide were analysed by the alkaline elution method. These individuals were occupied with the sterilization of medical devices in hospitals and in commercial plants. Ethylene oxide in the air of the working areas was detected up to a maximal concentration of 16.5 mg/m3 calculated as 4-h time-weighted average (4h TWA). Mean value was 1.47 +/- 0.52 mg/m3 (1 mg/m3 = 0.55 ppm). Compared to the mean elution rate of the DNA from non-smoking workers exposed to air concentrations of ethylene oxide below the detection limit of 0.1 mg/m3 (4h TWA) the non-smokers working in rooms with a concentration of ethylene oxide between 0.5 mg/m3 and 2 mg/m3 showed a statistically significant (P < 0.05) 119% higher mean elution rate and even for the non-smokers exposed to 0.1-0.5 mg/m3 of ethylene oxide a statistically significant (P < 0.05) 53% higher mean elution rate was observed. For smokers a similar tendency was found but the increase in elution rates in response to the external exposure was smaller than in non-smokers and no statistical significance was obtained. According to their sensitivity to ethylene oxide the non-smoking workers could be classified into two subpopulations. In the majority of the non-smokers (67%) approximately 5-fold more DNA strand breaks were induced by ethylene oxide than in the other non-smokers. A lowest detectable effect level could only be specified for non-smokers. (ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗
PubMed1994

Use of oligonucleotides containing ethenoadenine to study the repair of this DNA lesion. Determination of individual and collective repair activities.

Oligonucleotide duplexes of a defined sequence containing one 1,N6-ethenoadenosine (EA) were synthesized and used as substrates to study the repair of this DNA lesion in cell homogenates of peripheral mononuclear blood cells of 39 male and female workers, exposed to vinyl chloride. These data were compared to data from 39 employees of the same company working in other production plants and to data from a control group of 39 persons, living in an area without vinyl chloride production. After incubation of the 5'- and 3'-labeled oligonucleotide duplex with cell homogenate, a specific nicking activity, releasing the deoxyribosyl phosphate originally carrying the EA, was found. This activity was used to determine the individual and collective repair activities for ethenoadenine. The exposed group showed a mean of 158.5 +/- 39.9 (SD) fmol product fragment and did not differ significantly from the mean value of the two control groups with 156.5 +/- 42.9 fmol and 161.2 +/- 53.6 fmol, respectively. Large interindividual variations were found, ranging from 4.9-fold in the exposed to 8.2- and 7.2-fold in the control groups. The development of an assay for ethenoadenine repair is significant for understanding the role of EA repair in eukaryotic cells.

Adenine↗
PubMed1994

Regiospecific reduction of polycyclic aromatic quinones by rabbit liver dihydrodiol dehydrogenases.

Dihydrodiol dehydrogenase (DDH) isoenzymes were purified from rabbit liver (Klein et al., Eur. J. Biochem., 205 (1992) 1155), and the major forms CF-1, CF-5 and CM-2 were tested for their substrate specificity with dihydrodiol and quinone metabolites of polycyclic aromatic hydrocarbons. CF-5, which was shown to correspond to aldehyde reductase in rabbit liver, was found to efficiently oxidize aromatic dihydrodiol metabolites (phenanthrene-1,2-dihydrodiol, benz[a]anthracene-3,4-dihydrodiol) while CF-1, corresponding to carbonyl reductase, and CM-2 were much less active. All three enzyme forms were found to reduce polycyclic K-region o-quinones of benz[a]anthracene, chrysene and benzo[a]pyrene. CF-1 was the least active, and CM-2 was the most active form with reaction velocities of > 10 mumol/min.mg protein. Among a range of synthetic quinones tested, benz[a]anthracene-8,9-quinone and benzo[a]pyrene 9,10-quinone were also good substrates for the three enzymes, as well as p-benzoquinone and naphthalene-1,4-quinone. The reduction of polycyclic o-quinones, but not of p-benzoquinone, by enzyme CM-2 was accompanied by the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the formation of catechol metabolites from dihydrodiols and o-quinones may be catalyzed by the same enzymes in rabbit liver, and the reaction rate of the enzymatic reduction is strongly dependent on the structural type of the polycyclic quinone.

Alcohol Oxidoreductases↗
PubMed1994

Cigarette smoking protects mononuclear blood cells of carcinogen exposed workers from additional work exposure-induced DNA single strand breaks.

DNA single-strand breaks in mononuclear blood cells (MNC) of taxi drivers, painters, ethylene oxide-exposed sterilization workers, metal workers, and car mechanics were detected by alkaline filter elution and compared to smoking and non-smoking control persons. Cigarette smoking caused a small but statistically significant increase in control persons (13.5%). In all occupationally exposed groups except the car mechanics, statistically significant increases of DNA single-strand breaks were detected in non-smokers compared to non-smoking controls or comparing groups with high and low exposure. For non-smoking workers the increase in DNA single-strand breaks was found to be 22% for taxi drivers, 60% for painters, 70% for ethylene oxide-exposed workers, and 69% for metal workers compared to control persons. For smokers, however, the increase in DNA single-strand breaks caused by additional occupational exposure was smaller and did not reach statistical significance in any of the occupational groups investigated in this study. Since a high level of glutathione may help to detoxify electrophilic DNA-damaging agents we measured the concentration of total glutathione in MNC of smoking and non-smoking control persons. The glutathione concentration was 13% higher in smokers, but statistical significance was weak (p < 0.05; t-test). Thus cigarette smoking, which represents a highly significant risk factor in carcinogenesis by itself, protects on the other hand against some additional genotoxic insults.

Carcinogens↗
PubMed1994

Expression of L- and M2-pyruvate kinases in proliferating oval cells and cholangiocellular lesions developing in the livers of rats fed a methyl-deficient diet.

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.1% w/w DL-ethionine (CDE) for up to 22 weeks. The expression of the pyruvate kinase isoenzymes L (L-PK) and M2 (M2-PK) was immunohistochemically analyzed in liver slices from rats killed 4, 10, 14 and 22 weeks after starting the treatment. M2-PK was detected in bile duct epithelial cells of untreated rats and in proliferating oval cells, cholangiofibroses and cholangiofibromas of CDE-fed animals. Thus, M2-PK can be viewed as a positive marker of the bile duct epithelial/oval cell compartment. L-PK, a parenchymal cell-specific protein in untreated rat liver, was not present in proliferating oval cells, but was consistently observed in cells that were part of the ductal structures in the cholangiofibroses and cholangiofibromas. Based on their morphology, the L-PK-positive duct cells were undoubtedly part of the bile duct epithelial cell lineage and no L-PK-positive hepatocyte-like cells were observed in the ducts. Hence, this study clearly shows that the mere presence of a liver parenchymal cell marker in cells of the bile duct epithelial/oval cell compartment does not necessarily preclude that these cells are undergoing a differentiation into preneoplastic parenchymal cells, as has previously been suggested.

Animals↗
PubMed1994

Synthesis and mutagenicity of the diastereomeric fjord-region 11,12-dihydrodiol 13,14-epoxides of dibenzo[a,l]pyrene.

Extensive tumorigenicity studies in rodents revealed that dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen among all polycyclic aromatic hydrocarbons (PAHs) tested so far. The structure of the genotoxic metabolite(s) responsible for this exceptional carcinogenicity is unknown. The fjord-region syn- and anti-DB[a,l]P-11,12-dihydrodiol 13,14-epoxides (syn- and anti-DB[a,l]PDE) were synthesized to clarify their role as possible ultimate mutagenic and carcinogenic metabolites of DB[a,l]P.9-Formyl-11,12-dimethoxybenzo[g] chrysene was prepared from 9-phenanthrylacetic acid by a photochemical route. After reaction of the aldehyde with trimethylsulfonium iodide to generate an oxiranyl side-chain, treatment with boron trifluoride produced the key intermediate 11,12-dimethoxy-DB[a,l]P in 14% overall yield. From 11,12-dimethoxy-DB[a,l]P the syn- and anti-DB[a,l]PDE were stereoselectively prepared via the trans-11,12-dihydrodiol. The mutagenicity of the syn- and anti-DB[a,l]PDE was examined in four his- strains of Salmonella typhimurium and in Chinese hamster V79 cells. In all five test systems, the new dihydrodiolepoxides were more potent than any of the previously investigated dihydrodiolepoxides. The specific mutagenicity observed with anti-DB[a,l]PDE in strain TA104 exhibited the highest value ever found with any compound in any his- strains of S.typhimurium. The same appears to be true for the activity observed with this compound in V79 cells. In all five systems, syn-DB[a,l]PDE was only moderately less active than its anti-diastereomer (approximately 2-fold). The exceptional mutagenic activities of these dihydrodiolepoxides may be one of the reasons for the exceptional carcinogenic activity of DB[a,l]P.

Animals↗
PubMed1994

Substance-dependent sex differences in the activation of benzylic alcohols to mutagens by hepatic sulfotransferases of the rat.

Six primary and 10 secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons were tested for mutagenicity in Salmonella typhimurium TA98 in the presence of varying amounts of hepatic cytosol from adult male and female rats and 3'-phosphoadenosine-5'-phosphosulfate, the cofactor for sulfotransferases. With the exception of 1-(9-anthryl)ethanol, 4H-cyclopenta[def]-phenanthren-4-ol and 10-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, all the benzylic alcohols were activated to mutagens. For 1-(1-pyrenyl)ethanol (1-HEP), 1-(2-pyrenyl)ethanol (2-HEP), 6-hydroxymethylanthanthrene (6-HMAA), 2-hydroxymethylpyrene (2-HMP), 10H-indeno[1,2,7,7a-bcd]pyren-10-ol (OH-IP), 3-hydroxy-3,4-dihydrocyclopenta[cd]pyrene (3-OH-H2-CPcdP) and 1-(6-benzo[a]pyrenyl)ethanol (6-HEBP), this is the first observation of a mutagenic activity. The primary alcohols 1-hydroxymethylpyrene, 2-HMP, 9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene and 6-hydroxymethylbenzo[a]pyrene, as well as the secondary alcohols 1-HEP and 3-OH-H2-CPcdP, were more efficiently activated by hepatic cytosol from females than by preparations from males (2.6- to 8-fold). A further compound, 6-HEBP showed significant, but relatively weak, effects in the presence of cytosol from females, whereas it was inactive in the presence of hepatic cytosol from males. The reverse sex difference was observed in the activation of 4H-cyclo-penta[def]chrysen-4-ol, the activity of cytosol from males amounting to about four times that from females. Four other compounds, 2-HEP, 7-hydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, 6-HMAA and OH-IP, were activated with similar efficiency by hepatic cytosol from both sexes (< two-fold differences). The study indicates that different sulfotransferases are involved in the bioactivation of benzylic alcohols, including forms preferentially expressed in females as well as forms preferentially expressed in males, and that these enzymes qualitatively differ in their substrate tolerance for benzylic alcohols.

Animals↗
PubMed1994

Studies on the importance of microsomal epoxide hydrolase in the detoxification of arene oxides using the heterologous expression of the enzyme in mammalian cells.

In order to investigate the role of the microsomal epoxide hydrolase (mEH) in the detoxification of arene oxides in the presence of a high endogenous glutathione S-transferase (GST) activity-a situation found in several organs--we expressed the rat mEH cDNA in BHK21 Syrian hamster cells. These cells have high GST activities but contain an extremely low endogenous mEH enzyme activity. We obtained several cell clones which expressed the mEH heterologously, as determined by immunoblotting. The cell clone BHK21-mEH/Mz1 had the highest level of mEH protein. Immunofluorescence showed that the level of expression was almost homogeneous throughout the cell population. Total protein isolated from the cell line BHK21-mEH/Mz1 had a specific mEH activity of 123 pmol/min/mg protein, as determined with benzo[a]pyrene 4,5-oxide (B[a]P 4,5-oxide), which was 60 times higher than the activity in the parental cell line and eight times lower than the activity found in rat hepatocytes. However, BHK21-mEH/Mz1 cell homogenates were found to catalyze the conjugation of B[a]P 4,5-oxide to glutathione extremely well. The ratio of the GST enzyme activity to the mEH enzyme activity towards this substrate was 23 in the BHK21-mEH/Mz1 cell line. For hepatocytes this ratio was only six. Despite their already high potential to inactivate B[a]P 4,5-oxide by conjugation to glutathione, BHK21-mEH/Mz1 cells were better protected against the toxic and mutagenic effects of B[a]P 4,5-oxide than the parental cell line due to the expression of the mEH. The mEH, however, failed to protect the cells from the toxic and mutagenic effects of the bay region epoxide anti-7-methylbenz[a]anthracene-3,4-diol 1,2-oxide.

Animals↗