scholarly journals Epigenome modulated xenobiotic detoxification pathways control DMBA-induced breast cancer in agouti Avy/a mice

Epigenetics ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. 708-720 ◽  
Author(s):  
Simbarashe Mazambani ◽  
Madeleine Morris ◽  
Venugopalan Cheriyath
2005 ◽  
Vol 280 (23) ◽  
pp. 21867-21881 ◽  
Author(s):  
Scott R. Baerson ◽  
Adela Sánchez-Moreiras ◽  
Nuria Pedrol-Bonjoch ◽  
Margot Schulz ◽  
Isabelle A. Kagan ◽  
...  

Benzoxazolin-2(3H)-one (BOA) is an allelochemical most commonly associated with monocot species, formed from the O-glucoside of 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one by a two-step degradation process. The capacity of Arabidopsis to detoxify exogenously supplied BOA was analyzed by quantification of the major known metabolites BOA-6-OH, BOA-6-O-glucoside, and glucoside carbamate, revealing that detoxification occurs predominantly through O-glucosylation of the intermediate BOA-6-OH, most likely requiring the sequential action of as-yet-unidentified cytochrome P450 and UDP-glucosyltransferase activities. Transcriptional profiling experiments were also performed with Arabidopsis seedlings exposed to BOA concentrations, representing I50 and I80 levels based on root elongation inhibition assays. One of the largest functional categories observed for BOA-responsive genes corresponded to protein families known to participate in cell rescue and defense, with the majority of these genes potentially associated with chemical detoxification pathways. Further experiments using a subset of these genes revealed that many are also transcriptionally induced by a variety of structurally diverse xenobiotic compounds, suggesting they comprise components of a coordinately regulated, broad specificity xenobiotic defense response. The data significantly expand upon previous studies examining plant transcriptional responses to allelochemicals and other environmental toxins and provide novel insights into xenobiotic detoxification mechanisms in plants.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14093-e14093
Author(s):  
Mohamed Shanshal ◽  
Lukman Aderoju Tijani ◽  
Fred L. Hardwicke ◽  
Hassan Kaleem ◽  
Nicholas C. D'Cunha ◽  
...  

e14093 Background: Ral interacting protein (RLIP76) is a stress-responsive anti-apoptotic efflux transporter of the mercapturic acid pathway (MPy). The MPy enzymes are an essential component of the broader xenobiotic detoxification pathways (XDP) that are regulated by p53 (TP53) in response to xenobiotic/oxidative stress. Homozygous Rlip knockout (Rlip-/-) mice are resistant to benzopyrene induced adenocarcinoma and have constitutive activation of p53. The cancer-resistant phenotype of Rlip-/- mice is the diametric opposite of p53 homozygous knockout mice (p53-/-) mice, which die before the age of 24 weeks of spontaneous malignancy. Methods: Our preliminary studies show that creating Rlip deficiency through pharmacological or genetic methods caused all p53-/- mice to remain cancer-free at an unprecedented age of 32 weeks. This degree of cancer prevention has never been observed with any previous pharmacological or genetic intervention in p53-/- mice. Transcriptomic and epigenomic profiling of the cancer-free p53-/- mice revealed that the direction of change in expression of a network of Rlip-linked XDP enzymes and signaling proteins was identical to that in the cancer-resistant Rlip-/- mice. Results: We hypothesized that the activity of this Rlip-linked subset of the XDP enzymes/signaling proteins (designated XMN1) is a determinant of carcinogenic susceptibility caused by p53 loss. To examine this possibility, we queried the TCGA (The Cancer Genome Atlas) database to determine whether components of XMN1 were differentially expressed in human malignancy, and whether this was associated with overall survival. We focused on non-small cell lung cancer because of the high incidence of p53 mutations in these cancers. To our surprise, we found amplification or upregulation of XMN1 components conferred a reduced survival in lung adenocarcinoma but prolonged survival in squamous cell carcinoma. Conclusions: The mechanisms underlying this remarkable diametrically opposite effect on prognosis of are unknown and suggest opposed functions of XMN1 in Squamous verses Adenocarcinoma.


2005 ◽  
Vol 4 (11) ◽  
pp. 1686-1696 ◽  
Author(s):  
DaoHai Zhang ◽  
Lee Kian Tai ◽  
Lee Lee Wong ◽  
Lily-Lily Chiu ◽  
Sunil K. Sethi ◽  
...  

Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.


Author(s):  
John L. Swedo ◽  
R. W. Talley ◽  
John H. L. Watson

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.


2010 ◽  
Vol 34 (8) ◽  
pp. S49-S49
Author(s):  
Lei Wang ◽  
Xun Zhou ◽  
Lihong Zhou ◽  
Yong Chen ◽  
Xun Zhu ◽  
...  

2010 ◽  
Vol 34 (8) ◽  
pp. S47-S47
Author(s):  
Guopei Zheng ◽  
Sisi Yi ◽  
Yafei Li ◽  
Fangren Kong ◽  
Yanhui Yu ◽  
...  

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