High-performance liquid chromatographic assay of biphenyl metabolism by hepatocytes cultured in an embryo/hepatocyte co-culture medium

Ml, Mole; Sanders, Lee A.; La, Oglesby

doi:10.1016/0003-2697(88)90363-6

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…These microsomal oxidations were stimulated by the pretreatment of rats with 3-MC or phenobarbital. The differential effects of these inducers on the DP hydroxylations are in accordance with previous findings, 12,[26][27][28] and indicate that cytochrome P450 1A1/ 2 or 2B1 catalyze these hydroxylations. We confirmed that human cytochrome P450 1A2 and 2B6 expressed in human lymphoblastoid cells (Gentest, Woburn, MA, U.S.A.) catalyzed the oxidations of DP and DPP, respectively (data not shown).…”

Section: Discussionsupporting

confidence: 80%

“…4-Hydroxydiphenyl glucuronide and sulfate were reported to be formed by rat hepatocytes, or liver and kidney slices. 25,26) In the present study, we showed that DP, DPM and DPP are oxidized to the 4-hydroxyl derivatives, and in the case of DP to the 2-, and 3-hydroxyl derivatives as well, by cytochrome P450 of rat liver microsomes, and the 4,4′-dihydroxyl derivatives are also formed as minor metabolites. These microsomal oxidations were stimulated by the pretreatment of rats with 3-MC or phenobarbital.…”

Section: Discussionmentioning

confidence: 85%

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Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes

Kawa

Sanoh

Kohta

et al. 2003

JOURNAL OF HEALTH SCIENCE

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In this study, liver microsome-mediated activation of diphenyl (DP), diphenylmethane (DPM) and 2,2-diphenylpropane (DPP) to estrogens was demonstrated. These three compounds were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, they exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the cases of DP and DPM, or of phenobarbital-treated rats in the cases of DP and DPP, in the presence of NADPH. When these compounds were incubated with liver microsomes in the presence of NADPH, monohydroxyl and dihydroxyl derivatives were formed. These hydroxylated metabolites, 4-hydroxydiphenyl, 3-hydroxydiphenyl, 2-hydroxydiphenyl, 4-hydroxydiphenylmethane, 2-(4-hydroxyphenyl)-2-phenylpropane (4-OH-DPP), 4,4′-dihydroxydiphenyl, 4,4′-dihydroxydiphenylmethane and 2,2-bis(4-hydroxyphenyl)propane (bisphenol A), all exhibited estrogenic activity in MCF-7 cells. Binding assay of these hydroxylated compounds with rat uterus estrogen receptor was also positive. These results suggest that the estrogenic activities of DP, DPM and DPP were due to the formation of hydroxylated metabolites by the liver cytochrome P450 system.Key words ---diphenyl, estrogenic activity, metabolic activation, human breast cancer cell line MCF-7, endocrine disruption, cytochrome P450 exert biological effects. Many so-called xenoestrogens produce a wide variety of toxic effects in animals. They may be playing a role in the increasing incidence of hormonally related cancers such as breast cancer and testicular cancer, and other problems of the reproductive system in humans. It is therefore important to screen environmental contaminants for estrogenic activity. Their metabolites also need to be identified and screened. We recently showed that trans-stilbene, which is the parent compound of diethylstilbestrol, and trans-stilbene oxide were not estrogenic, but exhibited a potent estrogenic activity after metabolic activation by a liver microsomal oxidation system. 4,5) In that report, we suggested that the estrogenic activity was due to the hydroxylated metabolites, trans-4-hydroxystilbene and trans-4,4′-dihydroxystilbene, formed by cytochrome P450 1A1/2. Furthermore, we demonstrated that styrene oligomers were metabolically activated to estrogens by rat liver microsomes, especially cytochrome P450 2B1.6) These results demonstrate the importance of considering proestrogenic potential, when screening for xenoestrogens in the environment.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 85%

Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes

Kawa

Sanoh

Kohta

et al. 2003

JOURNAL OF HEALTH SCIENCE

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“…1, Sample). An explanation for these anomalies may lie in the composition of the sample solvent, which can have a significant impact on the chromatographic behavior of sample components, particularly those eluting early (12)(13)(14). The aberrant behavior observed is most likely due to a transient disturbance of chromatographic conditions introduced by injection of sample bolus into the fluid stream.…”

Section: Sample Oxidation Sample Purification and Chromatographic Mmentioning

confidence: 99%

Sample Preparation and High-Performance Liquid Chromatographic Analysis of Deoxyribonucleoside Triphosphates in Individual Rat Embryos

Mole

Hunter

Gao

et al. 1998

Analytical Biochemistry

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“…Among these chemicals, biphenyl is commonly used as a synthetic resin, as a heat transfer medium in manufacturing, and as a fungistatic agent for preserving fresh citrus fruits (11); the calculi induced by biphenyl are composed of its metabolites, such as 4-hydroxybiphenyl-o-sulfate (4-HBPOS) 1 (12), whereas the calculi induced by each of the other chemicals mentioned above are composed of themselves instead of their metabolites. In relation to these features, it should be noted that numerous studies on the metabolism of biphenyl have been reported (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Biphenyl is metabolized via multiple pathways, resulting in the production of various derivatives such as conjugates (sulfate and glucuronide) of 4-hydroxybiphenyl (4-HBP) and 4,4′-dihydroxybiphenyl (4,4′-DHBP) produced as major metabolites and conjugates of 2-hydroxybiphenyl (2-HBP), 3-hydroxybiphenyl (3-HBP), and 3,4-dihydroxybiphenyl (3,4-DHBP) produced as minor metabolites, but only the sulfate conjugate of 4-HBP is significantly involved in the formation of urinary calculi (12).…”

Section: Introductionmentioning

confidence: 99%

Sex Dependence of the Components and Structure of Urinary Calculi Induced by Biphenyl Administration in Rats

Ohnishi

Yajima

Yamamoto

et al. 2000

Chem. Res. Toxicol.

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To obtain definitive information about the mechanisms of urinary calculus formation and the structural characteristics of the calculi induced by biphenyl administration in rats, with a focus on the sex dependency, the constituents of the urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (ICP), micro Fourier transform infrared spectroscopy (mFT-IR), and ion chromatography (IC), and structural analyses were carried out by microscopy, mFT-IR, and the electron probe microanalyzer (EPMA) method. We attempted to account for the appreciably higher incidence of calculi in males than in females. mFT-IR analysis revealed that the biphenyl-induced urinary calculi in male rats are composed mainly of potassium 4-hydroxybiphenyl-o-sulfate (4-HBPOSK), whereas the calculi in female rats are composed mainly of 4-hydroxybiphenyl (4-HBP) and KHSO(4) produced by the hydrolysis of 4-HBPOSK. Observations of photomicrographs and the results of mFT-IR analysis indicated that the calculi in males have a multilayer structure consisting of alternating layers of 4-HBPOSK and calcium phosphate, whereas the calculi in females have no multilayer structure, but open holes in which needle-shaped crystals are present in some places. In view of the results of these analyses, including the EPMA analysis, it appears that calculus formation in males may involve a series of successive and irreversible reactions, whereas calculus formation in females may result from a series of reversible reactions, including the hydrolysis of 4-HBPOSK. It was inferred that the series of irreversible reactions involved in calculus formation in males is relatively more stable than that in the case of females, and thus, a sex difference in the reaction features may be responsible for the observed difference in the incidence of calculus formation.

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High-performance liquid chromatographic assay of biphenyl metabolism by hepatocytes cultured in an embryo/hepatocyte co-culture medium

Cited by 6 publications

References 17 publications

Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes

Metabolic Activation of Proestrogenic Diphenyl and Related Compounds by Rat Liver Microsomes

Sample Preparation and High-Performance Liquid Chromatographic Analysis of Deoxyribonucleoside Triphosphates in Individual Rat Embryos

Sex Dependence of the Components and Structure of Urinary Calculi Induced by Biphenyl Administration in Rats

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