hepatocarcinogen

γ-Glutamyl transpeptidase (GGT), a cell-surface enzyme, is strongly implicated in mammalian malignancy growth and migration processes including human hepatocarcinogens. However, simply and conveniently detect of GGT on the cell membrane remains highly challenging. In this study, a biotin-tagged fluorescent probe Nap-biotin-glu was developed using glutamic acid, naphthalimide, and biotin as the reaction site, fluorescent reporter, and membrane-targeting group, which required only three steps. Colocalization fluorescence imaging and immunofluorescence analysis indicated that probe Nap-biotin-glu was successfully realized in situ visualizing of GGT on the cell membrane...

In recent years, the incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide, in the context of an increasing prevalence of non-alcoholic fatty liver disease (NAFLD). In patients with diabetes mellitus, exogenous insulin is commonly prescribed and used in long-term settings. Recent studies suggest that insulin use may elevate the risk of HCC. A substantial body of work seeks to unpack the association between insulin use and the risk of developing HCC, although there may be conflicting evidence...

Bulbs ofLilium brownii, commonly known as "Bai-he" in China, serve both edible and medicinal purposes in clinical practice. In this study, two new isospirostanol-type saponins were isolated from L. brownii, and their structures were identified by spectroscopic method, and absolute configurations were elucidated by comprehensive analysis of spectral data obtained from combined acid hydrolysis. Two compounds were finally identified as 3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside]-(22R,25R)-5α-spirosolane-3β-ol (1) and 3-O-{α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-glucopyranoside}-(22R,25R)-5α-spirosolane-3β-ol (2), respectively...

PURPOSE: Oral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. MATERIALS AND METHODS: Gallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel...

BACKGROUND: Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non-selective β-blocker propranolol demonstrated antiproliferative activity in many cancer types. OBJECTIVE: This investigation aimed to evaluate the anticancer effect of propranolol against DEN-induced HCC in rats. METHODS: Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b...

Diethylnitrosamine (DEN) is a chemical hepatocarcinogenic agent that triggers a large array of oncogenic mutations after a single injection. Initiated hepatocytes subsequently undergo clonal expansion within a proliferative environment, rendering the DEN model a comprehensive carcinogen. In rodent studies, DEN finds extensive utility in experimental liver cancer research, mimicking several aspects of human hepatocellular carcinoma (HCC), including angiogenesis, metabolic reprogramming, immune exhaustion, and the ability to metastasize...

Methylcarbamate (MC), a reaction product between dimethyl dicarbonate and ammonia or ammonium ion, is a potent hepatocarcinogen in F344 rats. Various genotoxicity tests have shown negative results for MC. Although previous studies have described the effects of MC on the liver, including the formation of characteristic basophilic cytoplasmic inclusions (CIs) in hepatocytes, the toxicological significance of CIs and their involvement in hepatocarcinogenesis remain unclear. In the current study, to elucidate the mechanisms of MC hepatocarcinogenesis, we examined hepatotoxicity and genotoxicity after 4 weeks administration of MC using gpt delta rats with an F344 genetic background as a reporter gene transgenic animal model...

BACKGROUND: Traditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck ( C. limon ) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study . This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl4 /olive oil-induced HCC-like rats. MATERIALS AND METHODS: After preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods...

Aspergillus flavus produces hepatocarcinogenic aflatoxin that adversely impacts human and animal health and international trade. A promising means to manage preharvest aflatoxin contamination of crops is biological control, which employs non-aflatoxigenic A. flavus isolates possessing defective aflatoxin gene clusters to outcompete field toxigenic populations. However, these isolates often produce other toxic metabolites. The CRISPR/Cas9 technology has greatly advanced genome editing and gene functional studies...

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Biejia Jianwan (M-BJJW), a Traditional Chinese Medicine (TCM) decoction, has exhibited great potential in treating hepatocellular carcinoma (HCC). However, its underlying functional mechanism still remains unknown. AIM OF THE STUDY: The study aimed to explore the anti-hepatocarcinogenic effects of M-BJJW, specifically its influence on PD-L1-mediated immune evasion in hypoxic conditions, and elucidate the related molecular mechanisms in HCC...

Copper and zinc organometallics have multiple applications and many are considered "data-poor" because the available toxicological information is insufficient for comprehensive health risk assessments. To gain insight into the chemical prioritization and potential structure activity relationship, the current work compares the in vitro toxicity of nine "data-poor" chemicals to five structurally related chemicals and to positive DNA damage inducers (4-nitroquinoline-oxide, aflatoxin-B1). The HC-04 non-cancer human liver cell line was used to investigate the concentration-response effects (24 h and 72 h exposure) on cell proliferation, DNA damage (γH2AX and DNA unwinding assays), and epigenetic effects (global genome changes in DNA methylation and histone modifications using flow cytometry)...

The phosphorylated form of histone H2AX (γ-H2AX) serves as a commonly utilized biomarker for DNA damage. Based on our previous findings, which demonstrated the formation of γ-H2AX foci as a reliable biomarker for detecting bladder carcinogens in repeated dose 28-day study in rats, we hypothesized that γ-H2AX could also function as a biomarker for detecting hepatocarcinogens. However, we found that γ-H2AX foci formation was not effectively induced by hepatocarcinogens that did not stimulate hepatocyte proliferation...

Safrole oxide (SAFO), a metabolite of naturally occurring hepatocarcinogen safrole, is implicated in causing DNA adduct formation. Our previous study first detected the most abundant SAFO-induced DNA adduct, N7-(3-benzo[1,3] dioxol-5-yl-2-hydroxypropyl)guanine (N7γ-SAFO-G), in mouse urine using a well-developed isotope-dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (ID-HPLC-ESI-MS/MS) method. This study further elucidated the genotoxic mode of action of SAFO in mice treated with SAFO 30, 60, 90, or 120 mg/kg for 28 days...

SCOPE: Although many beneficial health effects are attributed to polyphenols their influence on the human metabolome has not been elucidated yet. The ubiquitous occurrence of polyphenols in the human diet demands comprehensive knowledge about physiological and toxicological effects of these compounds on human cells. METHODS AND RESULTS: The human hepatocarcinogenic cell line HepG2 is used to elucidate the effects of 13 polyphenols and three respective phenolic degradation products on the human metabolome using HPLC-MS/MS...

Direct DNA double-strand breaks result in phosphorylation of H2AX, a variant of the histone H2 protein. Phosphorylated H2AX (γH2AX) may be a potential indicator in the evaluation of genotoxicity and hepatocarcinogenicity. In this study, γH2AX and Ki-67 were detected in the short-term responses (24 hours after chemical administration) to classify genotoxic hepatocarcinogens (GH) from non-GH chemicals. One hundred and thirty-five 6-week-old Crl: CD(SD) (SPF) male rats were treated with 22 chemicals including 11 GH and 11 non-GH, sacrificed 24 hours later, and immunostained with γH2AX and Ki-67...

Elemicin, an alkenylbenzene flavoring, exists naturally in foods, herbs, and spices. Some alkenylbenzenes are hepatotoxic and hepatocarcinogenic in rodents. However, few studies have examined the toxicology of elemicin. In the current study, we comprehensively evaluated the general toxicity, genotoxicity, and carcinogenicity of elemicin using gpt delta rats and DNA adductome analysis. Groups of 10 male F344 gpt delta rats were treated with elemicin by gavage at a dose of 0, 25, 100, or 400 mg/kg bw/day for 13 weeks...

The secondary metabolites of polypropanoids, methyleugenol (MEG), and estragole (EG), found in many herbs and spices, are commonly used as food flavoring agents and as ingredients in cosmetics. MEG and EG have been reported to cause hepatocarcinogenicity in rodents, human livers, and lung cells. The formation of N 2 -dG and N 6 -dA DNA adducts is primarily attributed to the carcinogenicity of these compounds. Therefore, these compounds have been classified as "possible human carcinogens" by the International Agency for Research on Cancer and "reasonably anticipated to be a human carcinogen" by the National Toxicology Program...

Aflatoxin B1 (AFB1 ), a potent food-borne hepatocarcinogen, is the most toxic aflatoxin that induces liver injury in humans and animals. Species-specific sensitivities of aflatoxins cannot be fully explained by differences in the metabolism of AFB1 between animal species. The gut microbiota are critical in inflammatory liver injury, but it remains to reveal the role of gut microbiota in AFB1 -induced liver injury. Here, mice were gavaged with AFB1 for 28 days. Then, the modulation of gut microbiota, colonic barrier, and liver pyroptosis and inflammation were analyzed...

Herein, we present molecular nanoparticles of ferric-tannic complexes (so called ferric-tannic nanoparticles, FT NPs) used to enhance the MRI signal in the early stage of hepatocarcinoma. FT NPs were found to accumulate in the hepatic parenchyma without tumor nodules of Wistar rats in which hepatocarcinogenicity had been induced using diethylnitrosamine (DEN). The MRI enhancement and accumulation of FT NPs were clearly observed in the early phase of hepatocarcinogenicity, which was possibly modulated by various solute carrier family members present in the entire hepatic parenchyma of the DEN-induced rats...

We have developed an early detection method for bladder carcinogens with high sensitivity and specificity using immunohistochemistry of γ-H2AX, a well-known marker of DNA damage. To investigate the potential application of γ-H2AX as a biomarker for early detection of hepatocarcinogens, we examined γ-H2AX formation in the liver of rats treated with several different chemicals for 28 days. Six-week-old male F344 rats were orally treated for 28 days with five hepatocarcinogens: N-nitrosodiethylamine (DEN), di(2-ethylhexyl) phthalate, 1,4-dioxane (DO), 3,3'-dimethylbenzidine dihydrochloride, or thioacetamide (TAA), or with two non-hepatocarcinogens: 4-chloro-o-phenylenediamine and N-ethyl-N-nitrosourea...