Metabolism of polycyclic aromatic hydrocarbons to mutagenic species by rat and porcine ovarian granulosa cells: Detection by cocultivation with V79 Chinese hamster cells

Becedas, Luisa; Romert, Lennart; Toft, Erica; Jenssen, Dag; DePierre, Joseph W.; Ahlberg, Margot Bengtsson

doi:10.1016/0890-6238(93)90227-x

Cited by 15 publications

(6 citation statements)

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“…Therefore, our observation that DMBA induced apoptosis in cultured preovulatory follicles shows that these follicles are capable of metabolizing DMBA. This is consistent with previous studies, which showed that the major enzymes involved in PAH metabolism, CYP1A1, CYP1B1, microsomal epoxide hydrolase, and dihydrodiol dehydrogenase, are all expressed in rodent ovaries [52][53][54][55][56] and that cultured GCs obtained from preovulatory rat follicles are capable of metabolizing DMBA and BaP [57,58]. Metabolism of PAHs begins with oxidation to arene oxides, which can be hydrolyzed to dihydrodiols.…”

Section: Dmba Induces Apoptosis In Preovulatory Folliclessupporting

confidence: 92%

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Tsai-Turton

Nakamura

Luderer

2007

Biology of Reproduction

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The polycyclic aromatic hydrocarbon (PAH) 9,10-dimethyl-1,2-benzanthracene (DMBA) destroys primordial, primary, and secondary ovarian follicles in rodents, but its effects on antral follicles have received limited attention. PAHs are metabolized to reactive species, some of which can undergo redox cycling to generate reactive oxygen species (ROS). We previously showed that ROS initiate apoptosis in preovulatory follicles cultured without gonadotropin support and that glutathione (GSH) depletion induces apoptosis in the presence of gonadotropins. In the present study, we tested the hypothesis that DMBA induces apoptosis in preovulatory follicles, which is mediated by ROS and prevented by GSH. Preovulatory follicles were isolated from ovaries of 25-day-old rats 48 h after the injection of 10 IU of eCG and were cultured with DMBA in the presence of FSH for 2 to 48 h. DMBA induced granulosa cell (GC) and theca cell (TC) apoptosis at 48 h, as judged by TUNEL and activated caspase-3 immunostaining. DMBA treatment also increased the numbers of GCs and TCs that immunostained for the proapoptotic protein BAX. Follicular ROS levels were significantly increased in DMBA-treated follicles at 12, 24, and 48 h. GSH supplementation protected against and GSH depletion enhanced the induction of apoptosis in GCs and TCs by DMBA. These findings suggest that GSH is a critical protective mechanism against DMBA-induced apoptosis in antral follicles and that ROS generation may mediate DMBA-induced GC apoptosis.

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Section: Dmba Induces Apoptosis In Preovulatory Folliclessupporting

confidence: 92%

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Tsai-Turton

Nakamura

Luderer

2007

Biology of Reproduction

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“…The composition of the atmospheric particulate matter is of great concern to human health because its deposition in the respiratory tract has been related to several diseases. , These particles have been associated with the presence of adsorbed or absorbed polycyclic aromatic compounds (PACs), in particular with their oxidation products. − Studies have demonstrated that the oxidation products of PACs can be more harmful than the parent compound. ,, As a consequence, there is great interest in elucidating the transformation routes of adsorbed PACs. Acridine (Figure ), an aza-heterocyclic aromatic compound, is found in the troposphere as a result of the incomplete combustion of propane gas, diesel, and coal exhaust. , Due to the low value of its Henry's constant ( H = 4 × 10 -7 atm·m 3 /mol), it is readily adsorbed on atmospheric particulate matter …”

Section: Introductionmentioning

confidence: 99%

Characterization of Acridine Species Adsorbed on (NH₄)₂SO₄, SiO₂, Al₂O₃, and MgO by Steady-State and Time-Resolved Fluorescence and Diffuse Reflectance Techniques

2005

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The ground- and excited-state species of acridine adsorbed on (NH(4))(2)SO(4), SiO(2), Al(2)O(3), and MgO surfaces were investigated in order to determine the precursor species and electronic states responsible for acridine photodegradation on particles serving as models of atmospheric particulate matter. The species present on each solid surface were characterized by comparing the steady-state absorption and fluorescence spectra, time-resolved fluorescence, and absorption measurements on acridine in solution with those corresponding to adsorbed acridine. On silica, the ground-state species present were hydrogen-bonded, neutral, and protonated, while on alumina hydrogen-bonded and neutral species were identified. A comparison of the protonated acridine absorption and emission intensities on silica and alumina with those observed for acridine in acidic water demonstrated that the emission on the surfaces is higher than expected. This was interpreted as resulting from photoprotolytic reactions on silica and alumina. For acridine adsorbed on ammonium sulfate, protonated acridine was the only adsorbed species identified. Since, at a similar ground-state absorbance, the fluorescence intensity of acridine on ammonium sulfate was smaller than for acridine in acidic water, the quenching of the excited state or a rapid photochemical reaction with the surface was proposed. On magnesium oxide, the presence of neutral and hydrogen-bonded acridine species were characterized from the two-component analysis of the fluorescence, the triplet-triplet absorption decay curves, and the time-resolved emission spectra at different time delays. As demonstrated in these studies, acridine adsorbed species and their decay pathways depend on the acidic properties of these models of atmospheric particulate matter. In addition, a comparison of the photodegradation rates of acridine on the different solids tested is presented and discussed in terms of the nature of the species and their decay pathways.

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“…Studies have shown that DMBA can be metabolized by ovarian and placental microsomes (Bengtsson et al, 1983;Miyata et al, 2002). Furthermore, studies by Becedas et al (1993) suggest that rat granulosa cells in culture can metabolize DMBA to the carcinogen, 3,4-diol-1,2-epoxide. Collectively, these findings suggest that the ovary is capable of bioactivating DMBA to the 3,4-diol-1,2-epoxide.…”

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confidence: 99%

Involvement of Microsomal Epoxide Hydrolase Enzyme in Ovotoxicity Caused by 7,12-Dimethylbenz[a]anthracene

Rajapaksa

Sipes

Hoyer

2006

Toxicological Sciences

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Ovarian follicle disruption in mice caused by 7,12-dimethylbenz[a]anthracene (DMBA) is attributed to its bioactivation by CYP1B1 to a 3,4-epoxide which is then hydrolyzed to form a 3,4-diol by microsomal epoxide hydrolase (mEH). Further epoxidation by CYP1A1 or 1B1 forms the ultimate ovotoxicant, DMBA-3,4-diol-1,2-epoxide. Studies suggest that the mouse ovary expresses these enzymes, and thus, may be capable of bioactivating DMBA to its ovotoxic metabolite. The present study was designed to evaluate the role of ovarian mEH in DMBA-induced ovotoxicity using a novel neonatal mouse ovarian culture system. Ovaries from postnatal day (PND) 4 B6C3F(1) mice were incubated with DMBA (12.5 nM-1 microM) for various lengths of time. Following incubation, ovaries were histologically evaluated or assessed for mEH protein or mRNA. Following 15 days of incubation, DMBA reduced (p < 0.05) healthy follicles at concentrations >or= 12.5 nM. At 1 microM DMBA, follicle loss and increased mEH protein were measured (p < 0.05) by 6 h. mRNA encoding mEH markedly increased after 2 days of incubation, and this increase preceded accelerated follicle loss at 4 days. Furthermore, follicle loss induced by DMBA was prevented when cyclohexene oxide (2mM), an mEH inhibitor, was added to DMBA incubations. These studies suggest that the PND4 mouse ovary is capable of bioactivating DMBA to its ovotoxic form, and that ovarian mEH enzyme activity is likely involved. Furthermore, these observations support the use of a novel ovarian culture system to study ovary-specific metabolism of xenobiotic chemicals.

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Metabolism of polycyclic aromatic hydrocarbons to mutagenic species by rat and porcine ovarian granulosa cells: Detection by cocultivation with V79 Chinese hamster cells

Cited by 15 publications

References 15 publications

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Characterization of Acridine Species Adsorbed on (NH₄)₂SO₄, SiO₂, Al₂O₃, and MgO by Steady-State and Time-Resolved Fluorescence and Diffuse Reflectance Techniques

Involvement of Microsomal Epoxide Hydrolase Enzyme in Ovotoxicity Caused by 7,12-Dimethylbenz[a]anthracene

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Metabolism of polycyclic aromatic hydrocarbons to mutagenic species by rat and porcine ovarian granulosa cells: Detection by cocultivation with V79 Chinese hamster cells

Cited by 15 publications

References 15 publications

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Characterization of Acridine Species Adsorbed on (NH4)2SO4, SiO2, Al2O3, and MgO by Steady-State and Time-Resolved Fluorescence and Diffuse Reflectance Techniques

Involvement of Microsomal Epoxide Hydrolase Enzyme in Ovotoxicity Caused by 7,12-Dimethylbenz[a]anthracene

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Characterization of Acridine Species Adsorbed on (NH₄)₂SO₄, SiO₂, Al₂O₃, and MgO by Steady-State and Time-Resolved Fluorescence and Diffuse Reflectance Techniques