Changes of <i>c-Myc</i> and <i>DNMT1</i> mRNA and protein levels in the rat livers induced by dibutyl phthalate treatment

Urbanek-Olejnik, Katarzyna; Liszewska, Monika; Winczura, Alicja; Kostka, G.

doi:10.1177/0748233713512363

Cited by 7 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several groups reported on elevated expression of cyclins and/or the proto‐oncogene c‐myc in rat or murine liver when treated with PPARα ligands (Ma et al., 1997; Jolly et al., ; Urbanek‐Olejnik et al., ). Shah et al.…”

Section: Assessmentmentioning

confidence: 99%

“…Several groups reported on elevated expression of cyclins and/or the proto-oncogene c-myc in rat or murine liver when treated with PPARa ligands (Ma et al, 1997;Jolly et al, 2005;Urbanek-Olejnik et al, 2016). Shah et al (2007) described molecular mechanisms underlying the differences in c-myc regulation by human and murine PPARa.…”

Section: Liver Hypertrophy and Hyperplasiamentioning

confidence: 99%

See 1 more Smart Citation

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

311

265

View full text Add to dashboard Cite

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

show abstract

Section: Assessmentmentioning

confidence: 99%

Section: Liver Hypertrophy and Hyperplasiamentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

311

265

View full text Add to dashboard Cite

show abstract

“…Thottassery et al, 1992;Alsarra et al, 2006 47. Abdellatif et al, 1990;Abdellatif et al, 1991;Biegel et al, 2001 48. Cai et al, 1995;Kawashima et al, 1994 49.…”

unclassified

The PPARα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions

2017

View full text Add to dashboard Cite

A number of industrial chemicals and therapeutic agents cause liver tumors in rats and mice by activating the nuclear receptor peroxisome proliferator-activated receptor α (PPARα). The molecular and cellular events by which PPARα activators induce rodent hepatocarcinogenesis have been extensively studied elucidating a number of consistent mechanistic changes linked to the increased incidence of liver neoplasms. The weight of evidence relevant to the hypothesized mode of action (MOA) for PPARα activator-induced rodent hepatocarcinogenesis is summarized here. Chemical-specific and mechanistic data support concordance of temporal and dose-response relationships for the key events associated with many PPARα activators. The key events (KE) identified in the MOA are PPARα activation (KE1), alteration in cell growth pathways (KE2), perturbation of hepatocyte growth and survival (KE3), and selective clonal expansion of preneoplastic foci cells (KE4), which leads to the apical event-increases in hepatocellular adenomas and carcinomas (KE5). In addition, a number of concurrent molecular and cellular events have been classified as modulating factors, because they potentially alter the ability of PPARα activators to increase rodent liver cancer while not being key events themselves. These modulating factors include increases in oxidative stress and activation of NF-kB. PPARα activators are unlikely to induce liver tumors in humans due to biological differences in the response of KEs downstream of PPARα activation. This conclusion is based on minimal or no effects observed on cell growth pathways and hepatocellular proliferation in human primary hepatocytes and absence of alteration in growth pathways, hepatocyte proliferation, and tumors in the livers of species (hamsters, guinea pigs and cynomolgus monkeys) that are more appropriate human surrogates than mice and rats at overlapping dose levels. Despite this overwhelming body of evidence and almost universal acceptance of the PPARα MOA and lack of human relevance, several reviews have selectively focused on specific studies that, as discussed, contradict the consensus opinion and suggest uncertainty. In the present review, we systematically address these most germane suggested weaknesses of the PPARα MOA.

show abstract

“…2016 ). Dibutyl phthalate (DnBP) caused increased liver expression of DNMT1 in rats ( Urbanek-Olejnik et al. 2016 ).…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape

Paquette

MacDonald

Lapehn³

et al. 2021

Environ Health Perspect

View full text Add to dashboard Cite

Background: Phthalates are commonly used endocrine-disrupting chemicals that are ubiquitous in the general population. Prenatal phthalate exposure may alter placental physiology and fetal development, leading to adverse perinatal and childhood health outcomes. Objective: We examined associations between prenatal phthalate exposure in the second and third trimesters and the placental transcriptome at birth, including genes and long noncoding RNAs (lncRNAs), to gain insight into potential mechanisms of action during fetal development. Methods: The ECHO PATHWAYs consortium quantified 21 urinary phthalate metabolites from 760 women enrolled in the CANDLE study (Shelby County, TN) using high-performance liquid chromatography–tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate separate associations between maternal urinary phthalate metabolite concentration during the second and third trimester and placental gene expression at birth, adjusted for confounding variables. Genes were considered differentially expressed at a Benjamini-Hochberg false discovery rate (FDR) . Associations between phthalate metabolites and biological pathways were identified using self-contained gene set testing and considered significantly altered with an FDR-adjusted . Results: We observed significant associations between second-trimester phthalate metabolites mono (carboxyisooctyl) phthalate (MCIOP), mono-2-ethyl-5-carboxypentyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate and 18 genes in total, including four lncRNAs. Specifically, placental expression of NEAT1 was associated with multiple phthalate metabolites. Third-trimester MCIOP and mono-isobutyl phthalate concentrations were significantly associated with placental expression of 18 genes and two genes, respectively. Expression of genes within 27 biological pathways was associated with mono-methyl phthalate, MCIOP, and monoethyl phthalate concentrations. Discussion: To our knowledge, this is the first genome-wide assessment of the relationship between the placental transcriptome at birth and prenatal phthalate exposure in a large and diverse birth cohort. We identified numerous genes and lncRNAs associated with prenatal phthalate exposure. These associations mirror findings from other epidemiological and in vitro analyses and may provide insight into biological pathways affected in utero by phthalate exposure. https://doi.org/10.1289/EHP8973

show abstract

Changes of c-Myc and DNMT1 mRNA and protein levels in the rat livers induced by dibutyl phthalate treatment

Cited by 7 publications

References 31 publications

Risk to human health related to the presence of perfluoroalkyl substances in food

Risk to human health related to the presence of perfluoroalkyl substances in food

The PPARα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions

A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape

Contact Info

Product

Resources

About