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Time-course of transcriptomic change in the lungs of F344 rats repeatedly exposed to a multiwalled carbon nanotube in a 2-year test

ABSTRACT: Time-course of transcriptomic change in the lungs of F344 rats repeatedly exposed to a multiwalled carbon nanotube in a 2-year test

PROVIDER: PRJNA980209 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24833820_1.fastq.gz	Fastqsanger.gz
	SRR24833820_2.fastq.gz	Fastqsanger.gz
	SRR24833821_1.fastq.gz	Fastqsanger.gz
	SRR24833821_2.fastq.gz	Fastqsanger.gz
	SRR24833822_1.fastq.gz	Fastqsanger.gz

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Time-course of transcriptomic change in the lungs of F344 rats repeatedly exposed to a multiwalled carbon nanotube in a 2-year test

Project description:Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.

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Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test.

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Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.

Project description:Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to perform genome-wide mRNA profiling in mice blood to identify non-invasive blood based biomarkers for medical and occupational surveillance. The pathological results in this 1-year MWCNT post-exposure study was previously published in Snyder-Talkington et al. J Toxicol Environ Health A. 2016;79(8):352-66. doi: 10.1080/15287394.2016.1159635. Epub 2016 Apr 19. PMID: 27092743

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Expression profiling of mice exposed to multiwalled carbon nanotubes

Project description:Mice were aspirated with multiwalled carbon nanotubes in four doses ranging from 10 µg to 80 µg, plus control, and sacrificed after 1, 7, 28, and 56 days. RNA was extracted from the lungs and expression profilling by microarray was performed. This is a reference design two-color experiment. Each array was hybridized with RNA extracted from mouse lung labeled with Cy3, and universal reference RNA labeled with Cy5. Five different doses (0, 10ug, 20ug, 40ug, and 80ug) of multiwalled carbon nanotube aspiration were used and mice were sacrificed after 1, 7, 28, and 56 days. Eight replicates were used at each time/dose condition for a total of 160 arrays.

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Project description:Rattus norvegicus strain:F344 Raw sequence reads

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