Biomedical subjects

C S Yang

Publications and source records attributed to C S Yang.

At least 307 records · Page 17Linked to original sources

PubMed1991

Seroprevalence of anti-HCV among voluntary blood donors in Taiwan.

The epidemiologic characteristics of hepatitis C virus (HCV) infection among Chinese voluntary blood donors in 18 cities and counties all over the Taiwan Island were studied. Serum specimens of 1,135 randomly selected voluntary blood donors were tested for antibodies to HCV by Ortho enzyme-linked immunosorbent assay. A total of 18 donors were found to be positive for anti-HCV with a prevalence of 1.6%. Females had a higher prevalence (11/491 = 2.2%) than male (7/644 = 1.1%). The prevalence of anti-HCV for age groups of 18-30, 31-45 and 46-60 years was 2.0%, 0.8% and 0.0%, respectively, for males, as well as 1.7%, 2.0% and 5.0%, respectively, for females. Elevated serum alanine aminotransaminase (ALT) levels were highly associated with an increased anti-HCV prevalence (1.4% and 11.8% for those who had ALT level of less than or equal to 45 and greater than 45 IU/L) in all specimens tested. The HBsAg positivity rate was 4.5% in all specimens tested. There was no significant correlation between HBV and HCV infections. Although those who had a history of surgical operation, tatooing and ear piercing had a higher anti-HCV prevalence than those without such a history (2.8% vs. 1.2%, 4.0% vs. 1.5%, and 2.1% vs. 1.5%, respectively), the differences were not statistically significant. The prevalence was higher in Taipei (4.8%), Taichung (4.4%), Taoyuan (4.0%) than in other counties. The anti-HCV prevalence was 1.5% among qualified blood donors who had a ALT less than or equal to 45 IU/L and were negative on HBsAg, TPHA and anti-HIV tests.

Adolescent↗

PubMed1991

Analysis of Epstein-Barr virus DNA in nude mouse-passaged nasopharyngeal carcinoma tissues.

DNAs extracted from two series of nude mouse-passaged nasopharyngeal carcinoma (NPC) tissues, NPC-295 and -306, and P3HR1 cells were digested with restriction enzyme Bam HI, then electrophoresed on agarose gel and analysed for the Epstein-Barr virus (EBV) DNA fragments by Southern hybridization with 27 radioactive Bam HI DNA fragments and the Eco RI Dhet DNA fragment from cloned EBV DNA of B95-8 cell line. Constant hybridization patterns were revealed in these experiments and the results suggest a stable existence of EBV DNA including replicative form and episomal form in these tissues even after a long time of passage. Neither deletion in YH region nor in I region could be detected when using Bam HI Y, H and I as probes, suggesting the EBV in these tissues are "more complete" viruses. When Bam HI F was used as a probe, an extra Bam HI site was revealed in the analysis of the DNA from NPC-295 suggesting the polymorphism of DNA present in this region. Restriction maps of EBV DNAs in both nude mouse-passaged NPC tissues are proposed. The results suggest that nude mouse-passaged NPC tissue is a good model to study the structure of EBV DNA in tumor tissue.

Adult↗

PubMed1991

Hypersensitivity to acetate dialysate: report of a case.

Acetate dialysate is currently the most widely used in hemodialysis. The adverse effect of acetate during hemodialysis is well known upon the cardiovascular system. However, hypersensitivity reactions related to acetate during dialysis therapy are rare. We report a patient who developed hypersensitivity reactions such as generalized skin itching, flushing, hypotension and shortness of breath within a few minutes of beginning hemodialysis with acetate dialysate. Changing dialyzer membranes failed to alleviate these symptoms. Using the same dialyzer and tubing, these reactions disappeared immediately when bicarbonate dialysate was substituted for acetate dialysate. The patient's serum IgE and total eosinophile counts were normal. We conclude that acetate may initiate hypersensitivity reactions during hemodialysis. The exact mechanism is still unclear.

Acetates↗

PubMed1991

Molecular analysis of the p53 alleles in primary hepatocellular carcinomas and cell lines.

We have examined p53 oncogene/anti-oncogene alleles in 10 different human hepatoma cell lines and 18 primary hepatocellular carcinomas. The p53 allele in these hepatoma cell lines appears to be a frequent target of mutation as demonstrated by Southern and Northern blotting, immunoprecipitation and Western blot analysis. In general, the steady state level of p53 specific RNA or protein in these hepatoma cell lines is higher than in normal liver. However, in three out of ten cell lines, normal-sized p53 mRNA cannot be detected. In contrast, the involvement of the p53 allele in primary hepatocellular carcinoma appears to be an exceedingly rare event. Steady state levels of p53 specific RNA in primary hepatomas are practically indistinguishable from those in normal adult liver. Using the polymerase chain reaction technique, we have amplified and subcloned exons 5, 6, 7 and 8 of p53 from 10 different hepatoma samples. DNA sequence analysis of these exon subclones reveals no apparent structural alterations. Finally, synthesis of p53 specific mRNA or protein in a HepG2 human hepatoblastoma cell line does not appear to be affected by gene expression and replication of human hepatitus B virus. Surprisingly, unlike many other kinds of human solid tumors, point mutations in p53 do not appear to be important in primary tumors of hepatocellular carcinomas.

Alleles↗

PubMed1991

Enzyme mechanisms in the metabolism of nitrosamines.

Many nitrosamines are metabolized by cytochromes P450, one of which (P450IIE1) has received much attention because of its role in the metabolic activation of N-nitrosodimethylamine. This enzyme exists in man, rat, mouse, hamster and other animal species. It is inducible by fasting, diabetes and exposure to ethanol, acetone, isoniazid, benzene and other chemicals. P450IIE1 is responsible for the low Km form of N-nitrosodimethylamine demethylase and is the major enzyme catalysing the metabolic activation of this carcinogen. In addition, P450IIE1 is the most active P450 species known in the metabolism of N-nitrosoethylmethylamine and N-nitrosopyrrolidine. In the metabolism of N-nitrosobutylmethylamine, P450IIE1 preferentially oxidizes the methyl group over the butyl group, whereas P450IIB1 efficiently oxidizes both the methyl and butyl groups. P450IIB1 also catalyses the alpha-oxygenation of both the pentyl and methyl groups of N-nitrosopentylmethylamine, forming pentaldehyde and formaldehyde at a rate ratio of 2:1, as well as oxygenation at other carbons of the pentyl group. Many nitrosamines are effectively activated in nonhepatic target tissues. The metabolism of 4-(N-nitroso-methylamino)-1-(3-pyridyl)-1-butanone in lung and nasal microsomes is discussed.

Animals↗

PubMed1991

Enzyme kinetics of N-nitrosodimethylamine demethylase in rodents and humans.

A variety of Km values have been reported for hepatic microsomal N-nitrosodimethylamine demethylase (NDMAd). We demonstrated previously that the biologically important, high affinity (KmI) form of microsomal NDMAd is manifested by cytochrome P450IIE1 (also known as P450ac and P450j). The KmI value of NDMAd was, however, affected greatly by assay conditions: the possible presence of inhibitors and the presence of cytochrome b5. We re-examined the KmI value by testing the effect of enzyme concentrations and of different types of enzyme preparations on the Km. The KmI value ranged from 15 to 22 microM, as estimated by the direct linear plot, using a microsomal protein concentration in the range of 0.1 to 0.8 mg/ml with correction for substrate utilization. A slight yet significant dependency of microsomal protein concentration on the Km (r = 0890; p less than 0.05) was seen. When five different microsomal preparations were compared, the KmI value ranged from 14 to 24 microM (median, 20 microM), as estimated by the direct linear plot. The Km estimated by the commonly used Eadie-Hofstee plot did not differ from that by the direct linear plot. These Km values are close to the values obtained in studies with isolated cells and tissue slices. The KmI form of NDMAd (P450IIE1 and its orthologues) is present in rats, mice, rabbits, hamsters and guinea-pigs. It is responsible for the age-dependent differences between rats and hamsters and for the sex-related differences in mouse kidneys, and for the bioactivation and toxicity of NDMA. This enzyme also exists in human liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Human T-lymphotropic virus type I genome in adult T-cell leukemia/lymphoma.

The proviral DNA of human T-lymphotropic virus type I (HTLV-I) was examined in 8 patients with adult T-cell leukemia/lymphoma (ATL/L) by Southern blot analysis. Judging from the number of bands containing viral DNA sequences in tumor cells, one and three copies of proviral genome were detected in 7 and 1 cases, respectively. The proviral genome in 1 case contained variant PstI sites and a single defective provirus which lost 5' LTR, gag and a part of pol genes was found in 2 cases. However, the pX region was detected in both of 2 latter cases by using the polymerase chain reaction. The results indicate that not all tumor cells from ATL/L yield infectious viruses and also support that the product of pX region may contribute to the tumorigenesis of HTLV-I.

Adult↗

PubMed1991

[Studies on the toxic constituents of Illicium simonsii Maxim].

A new sesquiterpenelactone compound was isolated along with the known anisatin and shikimic acid from pericarps of the fruit of Illicium simonsii Maxim., family Magnoliaceae, collected in Sichuan province. This new sesquiterpene lactone compound exhibited high toxicity in mice. The structure of which was elucidated as 2-oxo-6-deoxyneoanisatin (I) based on spectral evidences. The detailed physical and chemical data were presented.

Animals↗

PubMed1990

Mouse renal cytochrome P450IIE1: immunocytochemical localization, sex-related difference and regulation by testosterone.

Cytochrome P450IIE1 is responsible for the metabolic activation of N-nitrosodimethylamine and a variety of other chemicals. Renal P450IIE1 was shown previously to be regulated by testosterone in C3H/HeJ and BALB/c mice. The present study investigated the distribution of cytochrome P450IIE1 in the kidneys of C3H/HeJ and BALB/c mice. The amount of P450IIE1 was immunotitrated by immunohistochemistry using polyclonal antibodies against rat P450IIE1. Strong immunoreactivity was identified mainly in the cortical tubules, including proximal tubules and some tubules. Weak immunoreactivity was also observed in the outer medulla when higher concentrations of antibodies were used. Much higher immunostaining was observed in male mice than in female mice when identical antibody dilutions were used. The renal P450IIE1 level in females was elevated to the same level as that in males 24 hr after administration of testosterone. The results showed a specific cellular localization of cytochrome P450IIE1 in mouse kidney. The findings may lead to a better understanding of the site-specific renal toxicity and carcinogenesis due to the activation of chemicals by cytochrome P450IIE1.

Animals↗

PubMed1990

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mouse lung microsomes and its inhibition by isothiocyanates.

The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lung tumors in rats, mice, and hamsters, and metabolic activation is required for the carcinogenicity. 2-Phenethyl isothiocyanate (PEITC), whose precursor gluconasturtiin (a glucosinolate) occurs in cruciferous vegetables, has been found to inhibit carcinogenesis by NNK. The purpose of the study was to investigate the enzymes involved in the metabolism of NNK in lung microsomes and to elucidate the mechanisms of inhibition of NNK metabolism by isothiocyanates. NNK metabolism in lung microsomes (isolated from female A/J mice) resulted in the formation of formaldehyde, 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol), 4-oxo-4-(3-pyridyl)butyric acid (keto acid), 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone, and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol, displaying apparent Km values of 5.6, 5.6, 9.2, 4.7, and 2540 microM, respectively. Higher Km values in the formation of formaldehyde and keto alcohol were also observed. When cytochrome P-450 inhibitors [2-(diethylamino)ethyl 2,2-diphenylpentenoate] hydrochloride (100 microM), carbon monoxide (90%), and 9-hydroxyellipticine (10 microM) were used, NNK metabolism was inhibited by each 70, 100, and 30%, respectively. Methimazole (1 mM), an inhibitor of the flavin-dependent monooxygenase, inhibited the formation of 4-(methyl-nitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol by 20%, but had no effect on the formation of keto alcohol. Inhibitory antibodies against cytochromes P-450IIB1 and -2, P-450IA1, and P-450IA2 inhibited the formation of keto alcohol by 25, 15, and 0%, respectively. Administration of PEITC at doses of 5 and 25 mumol/mouse 2 h before sacrifice produced a 40 and 70% decrease in microsomal NNK metabolism, respectively. PEITC and 3-phenylpropyl isothiocyanate exhibited a mixed type of inhibition, and the competitive component of inhibition had apparent Ki values of 90 and 30 nM, respectively. Preincubation of PEITC in the presence of a NADPH-generating system did not result in a further decrease in the formation of NNK metabolites, indicating that the metabolism of PEITC was not required for the inhibition. When a series of isothiocyanates with varying alkyl chain length (phenyl isothiocyanate, benzyl isothiocyanate, PEITC, 3-phenylpropyl isothiocyanate, and 4-phenylbutyl isothiocyanate) were used, the potency of the inhibition increased with the increase in chain length.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice.

Cytochrome P450IIE1 (P450IIE1) is responsible for the metabolic activation of N-nitrosodimethylamine (NDMA), a potent environmental carcinogen. This P450 enzyme displays a high-affinity NDMA demethylase (NDMAd) activity and is known to be induced by fasting and acetone administration. In the present work, the effects of pituitary hormones on the regulation of P450IIE1 in the liver were investigated and compared in rats and mice. There was no difference in liver microsomal NDMAd activity (nmol/min/mg protein) in rats in the intact (0.38 +/- 0.12), sham-operated (0.44 +/- 0.06), and hypophysectomized (0.52 +/- 0.04) groups. However, hypophysectomy caused a 2-fold increase in hepatic P450IIE1 protein levels as determined by immunoblot analysis. The P450IIE1 mRNA level in hypophysectomized rat was also significantly increased. The levels of blood ketone bodies (acetone, acetoacetate, and beta-hydroxybutyrate) were not different in the intact, sham-operated, and hypophysectomized groups, suggesting that ketone bodies are not involved in the induction of P450IIE1 protein and its mRNA by hypophysectomy. The discrepancy between the NDMAd activity and the increased P450IIE1 protein in rat liver by hypophysectomy can be partially explained by the lower hepatic NADPH-P450 reductase activity (50% that of the control) in the hypophysectomized rats. Upon the induction of liver NDMAd activity by fasting and acetone, hypophysectomy attenuated the effect of acetone but abolished the effect of fasting completely. Nevertheless, fasting still caused a 3-fold increase in the liver P450IIE1 mRNA level. An involvement of pituitary hormones in the regulation of liver microsomal P450IIE1 in mouse, however, was not observed. There was no difference in constitutive NDMAd activity between genetically growth hormone-deficient (lit/lit) mice and their phenotypically normal heterozygotes (lit/+). Fasting for 48 h caused 1.5- to 2-fold induction and acetone caused 2- to 3-fold induction, in both groups. The above changes in enzyme activity were due to the changes of P450IIE1 levels as verified by the immunoblot analysis. In male BALB/c mice, neither the hepatic NDMAd activity nor the P450IIE1 protein level was altered by hypophysectomy. The effects of acetone on the liver NDMAd activity were also similar in hypophysectomized and sham-operated mice. The results suggest that pituitary hormones are important in the regulation of the expression and activity of hepatic P450IIE1 in rats but not in the mouse strains investigated.

Acetone↗

PubMed1990

Expression of cytochrome P-450 enzymes in cultured human hepatocytes.

Hepatocytes from adult and newborn humans were put into primary culture and exposed to phenobarbital, 3-methylcholanthrene, or rifampicin, three well-known inducers of cytochrome P-450 in animals. The expression of four cytochrome P-450 enzymes (or groups of enzymes, namely P-450 IIIA, P-450 IIC8/9/10, P-450 IIE1, and P-450 IA2) was investigated. These enzymes were found to remain expressed during the period of culture studied. Treatment with the inducers for three days resulted in different responses, depending upon the inducer and the enzyme. Phenobarbital and rifampicin increased P-450 IIC8/9/10 mRNA transcripts and the corresponding protein, while 3-methylcholanthrene was ineffective. Both P-450 IIIA mRNA and protein were strongly induced by rifampicin. All of the hepatocytes were found to synthesize P-450 IIIA in response to rifampicin, as shown by immunoperoxidase staining. P-450 IIIA expression was not affected by phenobarbital and was decreased by 3-methylcholanthrene. P-450s IA2 and IIE1 decreased to 25-50% of the initial level during these cultures. P-450 IA2 and ethoxyresorufin O-deethylase activity (which is a monooxygenase activity related to P-450 IA family) were increased only by 3-methylcholanthrene and did not respond to the other inducers. P-450 IIE1 was not induced by any of these compounds. P-450 IIC8/9/10 and P-450 IIIA mRNA levels were also measured in human hepatocytes from one newborn. P-450 IIC8/9/10 was barely expressed in freshly isolated cells but increased dramatically with time in culture. P-450 IIIA transcripts were abundant in both freshly isolated and cultured cells derived from a newborn. These results clearly demonstrate that human hepatocytes continue to express cytochrome P-450 enzymes and respond to inducers in culture. This model system provides a useful approach for investigating the effects of drugs on maturation and expression of drug-metabolizing enzymes in human liver.

Adult↗

PubMed1990

Labeling index and labeling distribution of cells in esophageal epithelium of individuals at increased risk for esophageal cancer in Huixian, China.

The pattern of proliferation of epithelial cells in esophageal epithelium was studied by means of [3H]deoxythymidine labeling of esophageal epithelium in subjects from Huixian, Henan Province, China, a high-risk geographical region for esophageal cancer. Comparisons were made among patterns of cell proliferation observed in normal esophagus, in hyperplasia, in mild dysplasia, and in moderate dysplasia in a total of 118 subjects. The amount of cell proliferation observed was lowest in normal esophageal epithelium and increased progressively in subjects having hyperplasia, mild dysplasia, and moderate dysplasia. The location of proliferating cells was limited mainly to the base of the esophageal epithelium in normal esophagus, but expanded toward the surface of the esophageal lining in individuals with hyperplasia and dysplasia. The larger total numbers of proliferating cells in the esophageal epithelium and the progressive expansion of the proliferative compartment toward the epithelial surface found in hyperplasia and in dysplasia could both facilitate the screening of subjects for esophageal cancer risk and serve as intermediate biomarkers in prophylactic dietary or pharmacological intervention studies.

Cell Count↗

PubMed1990

Testosterone-mediated regulation of mouse renal cytochrome P-450 isoenzymes.

We have studied the extent to which mouse renal cytochrome P-450 isoenzymes are sexually differentiated, and the factor(s) regulating this dimorphism. Intriguingly, sex differences were not seen in the expression of a single cytochrome P-450 enzyme, but were observed in the expression of all P-450 isoenzymes detectable, encoded by six gene families or sub-families. This effect was mediated by testosterone, which had the capacity to both induce and repress P-450 gene expression, and which was independent of growth hormone. The changes in protein content were mirrored in all but one case by changes in the levels of mRNA, indicating that these genes contain hormone-responsive elements. These findings are consistent with numerous reports of sex differences in the susceptibility of the mouse kidney to the toxic and carcinogenic effects of drugs and environmental chemicals, many of which are metabolized to cytotoxic products by the cytochrome P-450-dependent mono-oxygenases. These data imply that circulating androgen levels will be an important factor in susceptibility of the kidney to toxic or carcinogenic compounds which require metabolic activation.

Animals↗

PubMed1990

Metabolic denitrosation of N-nitrosodimethylamine in vivo in the rat.

Enzymatic denitrosation is a potentially inactivating metabolic route that has been shown to convert carcinogenic N-nitrosodimethylamine (NDMA) to methylamine (MA) in vitro. To investigate its quantitative course in vivo, groups of 8-week-old male Fischer rats have been given small (8-15 mumol/kg) p.o. or i.v. bolus doses of 14C-labeled NDMA and the subsequent formation of radioactive MA has been monitored by high performance liquid chromatographic analysis of serially collected blood samples from each individual. Adjusting the [14C]MA fluxes observed for the previously measured rates at which MA is itself eliminated from the system after intragastric administration, denitrosation was calculated to represent a rather uniform 21.3 +/- 1.3% (SE) of total NDMA elimination in the four animals studied. By contrast, repetition of the experiment with fully deuterated NDMA (NDMA-d6) revealed a significantly wider variance in the results (39.8 +/- 8.9%). An alternative calculation using values for elimination of i.v. doses of MA and its trideuteromethyl analogue gave an even larger difference for MA formation between NDMA and NDMA-d6, the estimated extents of in vivo denitrosation in this case being 14.5 +/- 0.9% and 48.3 +/- 10.8%, respectively. The results indicate that denitrosation is a major metabolic pathway for NDMA elimination and suggest that deuteration of the carcinogen induces a shift in its metabolism toward increasing denitrosation at the expense of the competing activation pathway. Consequently, denitrosation may be the previously undefined in vivo metabolic route, the existence of which was suggested by the findings that deuteration of NDMA lowered its hepatocarcinogenicity and liver DNA alkylating ability in rats.

Animals↗

PubMed1990

Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities.

To elucidate the mechanisms by which thiamine deficiency affects hepatic microsomal monooxygenase activities, the effect of thiamine deficiency on two constitutive cytochrome P450 isozymes, P450IIE1 and P450IIC11, was investigated, using weanling male Sprague-Dawley rats. The clinical signs of thiamine deficiency were apparent after feeding a thiamine-deficient diet for 3 weeks. Thiamine deficiency caused an increase in P450IIE1, which was determined by N-nitrosodimethylamine demethylase assay and immunoquantitation of P450IIE1. This increase in the P450IIE1 level was mainly attributed to thiamine deficiency per se but not to dietary restriction. Ketone bodies were not elevated in thiamine-deficient rats, whereas ketone bodies were elevated and may have served as inducing factors in calorically restricted pair-fed animals. Injections of pyruvate or pyrithiamine in addition to thiamine deficiency did not potentiate the induction effect. On the other hand, thiamine deficiency did not affect the level of P450IIC11 during the 3 weeks of feeding the thiamine-deficient diet. In addition, thiamine deficiency increased cytosolic glutathione S-transferase activity but not steroid isomerase activity. The present study demonstrates the specificity of thiamine deficiency per se in the induction of P450IIE1 which does not involve an increase in the ketone body level.

Animals↗

PubMed1990

Metabolism of methyl tertiary-butyl ether by rat hepatic microsomes.

Exposure to methyl tertiary-butyl ether (MTBE), a commonly used octane booster in gasoline, has previously been shown to alter various muscle, kidney, and liver metabolic activities. In the present study, the metabolism of MTBE by liver microsomes from acetone- or phenobarbital-treated Sprague-Dawley rats was studied at concentrations of up to 5 mM MTBE. Equimolar amounts of tertiary-butanol, as measured by head-space gas chromatography, and formaldehyde were formed. The Vmax for the demethylation increased by 4-fold and 5.5-fold after acetone and phenobarbital treatments, respectively. The apparent Km value of 0.70 mM using control microsomes was decreased slightly after acetone treatment, but was increased by 2-fold after phenobarbital treatment. The metabolism of MTBE (1 mM) was inhibited by 35% by monoclonal antibodies against P450IIE1, the acetone/ethanol inducible form of cytochrome P450, suggesting a partial contribution by this isozyme. A single 18-h pretreatment of rats with 1 or 5 ml/kg MTBE (i.p.) resulted in a 50-fold induction of liver microsomal pentoxyresorufin dealkylase activity but no change in N-nitrosodimethylamine demethylase activity. These trends in activity agreed with immunoblot analysis which showed an elevation in P450IIB1 but no change in P450IIE1 levels.

Acetone↗

PubMed1990

Alteration of rat liver microsomal monooxygenase activities by gasoline treatment.

Previous work has shown an increase in rat liver enzyme activities after chronic exposure to gasoline vapor. In the present study, male Sprague-Dawley rats were pretreated with unleaded gasoline at 1 and 5 ml/kg, i.p., and selected hepatic microsomal monooxygenase activities were determined at 18, 48, and 72 h. At 18 h, moderate increases were observed in P450 content (1.3-fold), cytochrome c-reductase activity (1.25-fold), and in N-nitrosodimethylamine demethylation rate (1.25- to 1.6-fold). Pentoxyresorufin dealkylase activity (an activity displayed primarily by P450IIB1) was significantly elevated at 18 and 48 h (30- to 60-fold), and ethoxyresorufin dealkylase activity (an activity displayed by P450 IA1) was elevated (2- to 4-fold). Immunoblot analysis revealed no change in P450IIE1 at these time points, but an elevation in P450IIB1 in agreement with the pentoxyresorufin dealkylase activity measurements.

Animals↗