Genotoxicity of polychlorinated biphenyls (PCBs): recombinogenesis by biotransformation products

Butterworth, F. M.; Pandey, Pratibha; McGowen, Richard; Ali-Sadat, Shadan; Walia, Sandeep

doi:10.1016/0165-1218(95)90090-x

Cited by 28 publications

(10 citation statements)

References 34 publications

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“…These lowerchlorinated biphenyls have been shown to be metabolized into reactive intermediates capable of binding to DNA and/or inducing reactive oxygen species [Shimada et al, 1981;Butterworth et al, 1995;Amaro et al, 1996;Oakley et al, 1996Oakley et al, , 1997. In this study, a single treatment of rats with a polychlorinated biphenyl mixture (Aroclor 1242) resulted in adaptive effects, measured as increased liver weight and decreased prostate weight in the PCB-treated animals.…”

Section: Discussionmentioning

confidence: 99%

“…There is also evidence that PCBs might bind covalently, via metabolic activation, to cellular macromolecules as DNA, RNA, and protein [Wong et al, 1979;Narbonne and Daubeze, 1980;Shimada et al, 1981]. The initial step in the biotransformation of PCBs involves cytochrome P450 (CYP1A1, CYP1A2, and CYP2B1/2B2)-mediated oxidation to arene oxide intermediates [Preston et al, 1984], subsequently leading to dihydrodiols, catechols, and hydroquinones [Butterworth et al, 1995]. Peroxidase-dependent metabolism of these hydroquinones and catechols may lead via semiquinone intermediates to quinones, which were shown to be capable of binding covalently with DNA [Amaro et al, 1996;McLean et al, 1996;Oakley et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

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Induction of DNA adducts by several polychlorinated biphenyls

Schilderman

Maas

Pachen

et al. 2000

Environ. Mol. Mutagen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of DNA adducts by several polychlorinated biphenyls

Schilderman

Maas

Pachen

et al. 2000

Environ. Mol. Mutagen.

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“…Hydroxy metabolites of some lower chlorinated PCBs are known to be recombinogens (Butterworth et al, 1995). PCDDs may induce those cytochrome P450 isoforms responsible for the metabolic activation.…”

Section: Origin Of the Exposures And Nature Of The Genotoxinsmentioning

confidence: 99%

DNA Strand Length and EROD Activity in Relation to Two Screening Measures of Genotoxic Exposure in Great Lakes Herring Gulls

et al. 2005

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We collected tissues from herring gulls (Larus argentatus) nesting within and outside of the Great Lakes basin. Genotoxin exposure was assessed as fluorescent aromatic compounds (FACs) in bile and SOS Chromotest-inducing activity in muscle extracts. We determined whether these exposures were associated with decreased erythrocyte DNA strand length and/or induction of hepatic ethoxyresorufin-O-deethylase (EROD) activity. FACs were detected in all bile samples. Most muscle extracts produced a positive or marginal SOS response in the presence of S9. SOS induction potentials were strongly associated with dietary trophic level. The median molecular length of DNA isolated from erythrocytes for 14 of 17 adult and 10 of 11 prefledgling collections was reduced compared to the modal class for their respective age group suggesting widespread DNA damage. DNA damage was greatest in gulls from Saginaw Bay, Lake Huron. Median EROD activity in both adults and prefledglings from remote locations was significantly lower than that of gulls from the lower Great Lakes and was not associated with concentrations of benzo[a]pyrene (B[a]P)-like FACs. Our results indicate Great Lakes herring gulls were exposed to genotoxins and Ah-receptor activating agents in biologically significant concentrations in the early 1990s. These agents appear to be persistent bioaccumulative compounds and/or their metabolites.

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“…It may be significant that VGLUTs belong to a larger family, including transporters that localize to the plasma membrane and lysosomes (12,(43)(44)(45). VGLUTs also sort to SLMVs and SVs via an AP3-dependent pathway (19,46); because VMATs are unable to sort to SLMVs in PC12 cells (47,48), it is possible that VMATs, unlike VGLUTs, cannot access the AP3-dependent pathway.…”

Section: Linementioning

confidence: 99%

A Tyrosine-based Motif Localizes a Drosophila Vesicular Transporter to Synaptic Vesicles in Vivo

Grygoruk¹,

Fei²,

Daniels

et al. 2010

Journal of Biological Chemistry

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Vesicular neurotransmitter transporters must localize to synaptic vesicles (SVs) to allow regulated neurotransmitter release at the synapse. However, the signals required to localize vesicular proteins to SVs in vivo remain unclear. To address this question we have tested the effects of mutating proposed trafficking domains in Drosophila orthologs of the vesicular monoamine and glutamate transporters, DVMAT-A and DVGLUT. We show that a tyrosine-based motif (YXXY) is important both for DVMAT-A internalization from the cell surface in vitro, and localization to SVs in vivo. In contrast, DVGLUT deletion mutants that lack a putative C-terminal trafficking domain show more modest defects in both internalization in vitro and trafficking to SVs in vivo. Our data show for the first time that mutation of a specific trafficking motif can disrupt localization to SVs in vivo and suggest possible differences in the sorting of VMATs versus VGLUTs to SVs at the synapse. During synaptic vesicle (SV)3 biogenesis, synaptic vesicle components traffic to the plasma membrane for assembly into mature synaptic vesicles (1, 2). In most current models, vesicles must undergo an internalization step at the plasma membrane to complete SV biogenesis. In addition, SV recycling requires endocytosis, and multiple modes of endocytosis may occur at the synapse (3). Genetic studies indicate that SVs cannot form in the absence of critical elements of the endocytic machinery (4 -7). It remains surprisingly unclear, however, how particular trafficking motifs sort proteins to SVs. Although it is thought that endocytic motifs in vesicular proteins such as vesicular neurotransmitter transporters are likely to be required for their localization to SVs (8), this critical idea has never been explicitly tested in an intact animal. Moreover, it remains unclear whether all vesicular proteins use the same trafficking motifs and pathways to sort to SVs. Here, we have begun to investigate these questions in Drosophila using two structurally divergent vesicular neurotransmitter transporters.Vesicular transporters are required for the transport of neurotransmitter into the lumen of SVs and include specific transporters for acetylcholine (9), ␥-aminobutyric acid and glycine (10, 11), glutamate (12), and monoamines (9). In vitro trafficking studies of the neural isoform of mammalian VMAT (VMAT2) have shown that an Ile-Leu (dileucine) sequence within the cytoplasmic C terminus is necessary for endocytosis in PC12 cells and hippocampal neurons (13,14) and localization to synaptic-like microvesicles (SLMVs) in PC12 cells (15). A dileucine and possibly an additional tyrosine-based motif in rat VAChT allows internalization from the cell surface and localization to SLMVs in neuroendocrine cells (16 -18). A variant of the dileucine motif (FV) as well as a polyproline motif have been proposed to allow internalization of VGLUT1 and recycling to SVs in cultured neurons (19 -21).Although much is known about the function of transporter trafficking motifs in vitro, the role of ...

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Genotoxicity of polychlorinated biphenyls (PCBs): recombinogenesis by biotransformation products

Cited by 28 publications

References 34 publications

Induction of DNA adducts by several polychlorinated biphenyls

Induction of DNA adducts by several polychlorinated biphenyls

DNA Strand Length and EROD Activity in Relation to Two Screening Measures of Genotoxic Exposure in Great Lakes Herring Gulls

A Tyrosine-based Motif Localizes a Drosophila Vesicular Transporter to Synaptic Vesicles in Vivo

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