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Kerr, Mia A.; Nasca, Philip C.; Mundt, Kenneth A.; Michalek, Arthur M.; Baptiste, Mark S.; Mahoney, Martin C.

doi:10.1023/a:1008951632482

Cited by 58 publications

(7 citation statements)

References 16 publications

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“…Moreover, it has been reported that exposure of pregnant rats to dioxin reduces AHR expression levels in the fetus [43]. In addition, it has been reported that children of parents with dioxin exposure may be at increased risk of NB [44]. In this study, we demonstrated an inverse relationship between AHR and MYCN expression both in vitro and in vivo .…”

Section: Discussionsupporting

confidence: 62%

Aryl Hydrocarbon Receptor Downregulates MYCN Expression and Promotes Cell Differentiation of Neuroblastoma

Liao

Juan

et al. 2014

PLoS ONE

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Neuroblastoma (NB) is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. In this study, we aimed to investigate novel MYCN-related genes and assess how they affect NB cell behavior. The different gene expression found in 10 MYCN amplification NB tumors and 10 tumors with normal MYCN copy number were analyzed using tissue oligonucleotide microarrays. Ingenuity Pathway Analysis was subsequently performed to identify the potential genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, was found to be inversely correlated with MYCN expression in NB tissues. This correlation was confirmed in a further 14 human NB samples. Moreover, AHR expression in NB tumors was found to correlate highly with histological grade of differentiation. In vitro studies revealed that AHR overexpression in NB cells induced spontaneous cell differentiation. In addition, it was found that ectopic expression of AHR suppressed MYCN promoter activity resulting in downregulation of MYCN expression. The suppression effect of AHR on the transcription of MYCN was compensated for by E2F1 overexpression, indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore, AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings suggest that AHR is one of the upstream regulators of MYCN. Through the modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect NB differentiation.

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Section: Discussionsupporting

confidence: 62%

Aryl Hydrocarbon Receptor Downregulates MYCN Expression and Promotes Cell Differentiation of Neuroblastoma

Liao

Juan

et al. 2014

PLoS ONE

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“…In studies that reported on maternal occupational exposures in pregnancy, positive associations have also been reported for exposure to acetone and insecticides and neuroblastoma (Kerr et al, 2000). Similar to the present study, no associations were previously observed with maternal occupational exposure to diesel fuel nor with maternal employment as a mechanic or service station attendant (De Roos et al, 2001; Olshan et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…There are not previous reports, to our knowledge, of neuroblastoma in relation to PAH exposure. However, other studies have reported elevated effect estimates for maternal occupational exposures that involve PAH exposure, such as petroleum, creosote, and coal soot (Kerr et al, 2000). Its role as a developmental toxicant is supported by evidence that inhalation exposure of PAH causes reduced fetal growth and adduct formation in cord blood (Perera et al, 2005; Tang et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…There is some suggestion of increased risks with low birthweight, paternal smoking, and maternal pregnancy intake of alcohol or certain prescription medications (Heck et al, 2009). Previous studies have additionally suggested increased risk for neuroblastoma with parental occupational exposure to wood dusts, hydrocarbons, pesticides, lead, petroleum, coal tar and soot (Kerr et al, 2000; Olshan et al, 1999). Given that a fetus is more vulnerable to environmental exposures in comparison to an adult, pregnancy exposures to air toxins may contribute to risk (Selevan et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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An exploratory study of ambient air toxics exposure in pregnancy and the risk of neuroblastoma in offspring

Heck

Park

Qiu³

et al. 2013

Environmental Research

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Little is known about the etiology of neuroblastoma, the most common cancer in infancy. In this study, we examined maternal exposure to ambient air toxics in pregnancy in relation to neuroblastoma in the child. We ascertained all cases of neuroblastoma listed in the California Cancer Registry 1990-2007 that could be linked to a California birth certificate, and controls were selected at random from California birth records. Average air toxics exposures during pregnancy were determined based upon measures from community-based air pollution monitors. The study included 75 cases and 14,602 controls who lived with 5 kilometers of an air pollution monitor, and we additionally examined results for those living within a smaller radius around the monitor (2.5 km). Logistic regression was used to determine the risk of neuroblastoma with one interquartile range increase in air toxic exposure. Neuroblastoma risk was increased with higher maternal exposure to carbon tetrachloride (OR=2.65, 95%CI 1.07, 6.53) and polycyclic aromatic hydrocarbons (OR=1.39, 95%CI 1.05, 1.84), particularly indeno(1,2,3-cd)pyrene and dibenz(a,h)anthracene. Hexavalent chromium was associated with neuroblastoma at the 5 km distance (OR=1.32, 95%CI 1.00, 1.74) but not at the 2.5 km distance. This is one of the first studies to report associations between neuroblastoma and these air toxics.

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“…Malignancies potentially associated with occupational coal tar pitch exposure include lung and prostate cancer in coke oven workers, lung cancer in foundry workers, lung and bladder cancer in aluminum smelter workers, and lung and stomach cancer in roofers (Harrison 2004). Other cancers suggested as being related to these compounds include renal cell carcinoma (Steineck et al 1989), neuroblastoma (following parental occupational exposure) (Kerr et al 2000), and non-Hodgkin lymphoma (Persson et al 1989). The International Agency for Research on Cancer (IARC) has concluded that there is “sufficient” evidence for coal tar pitch (IARC 1998a) to be considered carcinogenic in humans, but that creosotes (IARC 1998b) have only “limited evidence” for human carcinogenicity, despite demonstrating “sufficient” evidence to establish carcinogenicity in animals.…”

Section: Discussionmentioning

confidence: 99%

Squamous Cell Carcinoma of the Skin and Coal Tar Creosote Exposure in a Railroad Worker

Carlsten

Hunt

Kaufman

2005

Environ Health Perspect

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A 50-year-old male railroad worker presented to his primary care physician with an erythematous, tender skin lesion on the right knee; a biopsy of this lesion revealed squamous cell carcinoma in situ. The site of the lesion was sun-protected but had been associated with 30 years of creosote-soaked clothing. In this article, we review dermal and other malignancies associated with creosote, along with creosote occupational exposures and exposure limits. This is a unique case, given the lack of other, potentially confounding, polyaromatic hydrocarbons and the sun-protected location of the lesion.

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Abstract: Due to the uncertainty of the biologic plausibility of these associations and the possibility of alternative explanations, these results should be interpreted cautiously.

Cited by 58 publications

References 16 publications

Aryl Hydrocarbon Receptor Downregulates MYCN Expression and Promotes Cell Differentiation of Neuroblastoma

Aryl Hydrocarbon Receptor Downregulates MYCN Expression and Promotes Cell Differentiation of Neuroblastoma

An exploratory study of ambient air toxics exposure in pregnancy and the risk of neuroblastoma in offspring

Squamous Cell Carcinoma of the Skin and Coal Tar Creosote Exposure in a Railroad Worker

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