Pathology of the Liver and Gallbladder

Maronpot, Robert R.; Malarkey, David E.

doi:10.1007/978-1-4939-9777-0_4

Cited by 3 publications

(5 citation statements)

References 27 publications

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“…For all animals, similar treatment‐related lesions were distributed throughout the liver section at each respective timepoint. At 14 days, hepatocytes were hypertrophied, a common adaptive cellular response following administration of a xenobiotic (Maronpot & Malarkey, 2019) along with evidence of oval cell proliferation. By 90 days, there was marked dissemination of preneoplastic clear cell foci in AFB1‐treated rats.…”

Section: Resultsmentioning

confidence: 99%

“…A single adenoma was identified at 90 days, and no carcinomas were present in the sub‐chronic exposed groups. Because foci are rarely observed in any rat strains in short‐term (90‐day) toxicity studies (Maronpot & Malarkey, 2019), the presence of numerous foci of cellular alteration secondary to AFB1 treatment is important as foci are postulated to predispose the development of adenomas and carcinomas (Maronpot & Malarkey, 2019; Thoolen et al, 2010). Livers from control dose fed animals were within normal limits across all timepoints.…”

Section: Resultsmentioning

confidence: 99%

“…cellular response following administration of a xenobiotic(Maronpot & Malarkey, 2019) along with evidence of oval cell proliferation. By 90 days, there was marked dissemination of preneoplastic clear cell foci in AFB1-treated rats.…”

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confidence: 99%

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Whole exome and transcript profiling of liver following aflatoxin B1 exposure in rats

Foley

Elgart

Phadke

et al. 2023

J of Applied Toxicology

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We recently developed a rat whole exome sequencing (WES) panel and used it to evaluate early somatic mutations in archival liver tissues from F344/N rats exposed to the hepatocarcinogen, Aflatoxin B1 (AFB1), a widely studied, potent mutagen and hepatocarcinogen associated with hepatocellular carcinoma (HCC). Rats were exposed to 1-ppm AFB1 in feed for 14, 90, and 90 days plus a recovery 60-day, nonexposure period (150-day) timepoint. Isolated liver DNA was exome sequenced. We identified 172 sequence variants across all timepoints, of which 101 were nonsynonymous variants. Well-annotated genes carried a diverse set of 29 nonsynonymous mutations at 14 days, increasing to 39 mutations at 90 days and then decreasing to 33 mutations following the 60-day recovery. Gene Set Enrichment Analysis conducted on previously reported, available RNA expression data of the same exome sequenced archival samples identified altered transcripts in pathways associated with malignant transformation. These included HALLMARK gene sets associated with cell proliferation (MYC Targets Version 1 and Version 2, E2F targets), cell cycle (G2M checkpoint, mitotic spindle), cell death (apoptosis), and DNA damage (DNA repair, UV response Up, Reactive oxygen species) pathways. DriverNet Impact analysis integrated exome-seq and expression data to reveal somatic mutations in Mcm8, Bdp1, and Cct6a that may drive cancer formation. Connectivity with transcript expression changes identified these genes as the top-ranked candidate driver genes associated with hepatocellular transformation. In conclusion, exome sequencing revealed early somatic mutations that may play a role in cancer cell transformation that are translatable to aflatoxin-induced HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Whole exome and transcript profiling of liver following aflatoxin B1 exposure in rats

Foley

Elgart

Phadke

et al. 2023

J of Applied Toxicology

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“…It is because the cell cannot eliminate water so that it accumulates in the cell, causing the cell organelles to absorb water and swell. 30 Necrosis appears in 3 patterns: karyolysis (missing cell nucleus), pyknosis (black cell nucleus), and karyorrhexis (cell nucleus blurring or cracking). 31 This study found that the number of cell death (necrosis) <10% in the dose group 7 and 35 mg/kg BW on the 8 th , 15 th , and 22 nd days and at a dose of 150 mg/kg BW on the 8 th day.…”

Section: Discussionmentioning

confidence: 99%

Subacute Toxicity Test of Hydrocotyle Sibthorpioides Lam. Extract on Histopathological Images of Liver and Kidney of White Male Mice

A¹,

Abdillah²,

Husni³

et al. 2022

Pharmacogn J.

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“…Hemangiosarcoma originating from liver has an irregular perimeter, which may be either raised or depressed when near the surface of the liver. Histologically, tumor cells may form solid masses, and necrosis and thrombosis are also frequently present 15 . These features do not correspond with this case.…”

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confidence: 99%

Metastatic hemangiosarcoma of the liver in a young rat

2017

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Spontaneous hemangiosarcoma is generally uncommon in rats. Furthermore, there are only a few case reports in young rats. This report describes a spontaneous hemangiosarcoma in a young 7-week-old rat. At necropsy, no remarkable changes were noted in any organs including the liver. Histopathologically, multifocal small tumors were located mainly in the perilobular region of the liver. The tumors comprised polygonal to short spindle-shaped cells that showed cellular atypia and local infiltration. In the foci, there were blood-filled spaces lined by spindle-shaped cells. Reticular fibers, which were loosely connected together and formed an irregular network within the foci, were noticed with Azan and silver stain. Immunohistochemistry revealed that tumor cells expressed vascular endothelial cell markers: von willebrand factor and CD34, respectively. These features indicate that the tumor originated from vascular endothelial cells. Although the primary lesion was uncertain, the foci were all small and multicentrically located mainly in the perilobular region, indicating that the liver lesion likely formed by hematogenic metastasis. Taken together, we diagnosed this case as a metastatic hemangiosarcoma.

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Pathology of the Liver and Gallbladder

Cited by 3 publications

References 27 publications

Whole exome and transcript profiling of liver following aflatoxin B1 exposure in rats

Whole exome and transcript profiling of liver following aflatoxin B1 exposure in rats

Subacute Toxicity Test of Hydrocotyle Sibthorpioides Lam. Extract on Histopathological Images of Liver and Kidney of White Male Mice

Metastatic hemangiosarcoma of the liver in a young rat

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