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Performance of 181 chemicals in a Drosophila assay predominantly monitoring interchromosomal mitotic recombination.

An evaluation is presented of the effects of 181 chemicals in the (white/white+) (w/w+) eye mosaic assay, an in vivo short-term test measuri … d V) belonging to this category mainly represented four distinct types. (a) Procarcinogens, such as 2-acetylaminofluorene, dibenz[a,h]anthracene, p-dimethylaminoazobenzene, 2-naphthylamine and safrole, for which metabolic conversion was the apparent problem in the assay. (b) Electrophilic chemicals of high nucleophilic selectivity: acrolein, acrylamide, acrylonitrile, …

Mitochondrial carnitine palmitoyl transferase-II inactivity aggravates lipid accumulation in rat hepatocarcinogenesis.

AIM: To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase II (CPT-II) expression during malignant transformation of rat hepatocytes. METHODS: Sprague-Dawley male rats were fed with normal, high fat (HF), and HF containing 2-fluorenylacetamide (2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, precancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-II alterations were analyzed by immunohistochemistry, and compared with CPT-II specific concentra

Somatic cell mutagenicity in Drosophila melanogaster in comparison with genetic damage in early germ-cell stages.

With the intention of assessing the general performance, sensitivity and the underlying mechanisms of somatic cell mutagenicity assays in Dr … d mutations in white/white-coral larvae, as opposed to only weak effects in early germ-cell stages. 2-Acetylaminofluorene (2AAF) showed marginal effects in both germ cells and somatic tissue after exposure of female larvae, but was inactive in testis. The discrepancy in mutational response between somatic cells and premeiotic germ cells is most impressive for MMS and B …

Stromal cell derived factor-1 enhances bone marrow mononuclear cell migration in mice with acute liver failure.

AIM: To evaluate the number of bone marrow mononuclear cells (BMMC) that are migrated to the liver following transplantation of murine BMMC into mice with acute liver injury. METHODS: BMMC were isolated from the bone marrow of mice in a lymphocyte separation medium and then labeled with PKH26. The labeled cells were subsequently infused into the caudal veins of BALB/c mice with hepatic injury induced by carbon tetrachloride and 2-acetylaminofluorene. Mice in experimental group were treated with stromal cell-derived factor-1 (SDF-1) which was injected intraperitoneally after transplantation of…

Potential effect of sodium nitrite on the expression of nuclear proto-oncogenes during 2-acetyl aminofluorene-induced hepatocarcinogenesis in rats.

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were treated with NaNO2 (0.3%); group III was given 0.02% AAF alone; groups IV and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in their diet for 12 weeks. At the end of the

Reconstitution of yeast nucleotide excision repair with purified Rad proteins, replication protein A, and transcription factor TFIIH.

Nucleotide excision repair (NER) functions to remove DNA damage caused by ultraviolet light and by other agents that distort the DNA helix. The NER machinery has been conserved in structure and function from yeast to humans, and in humans, defective NER is the underlying cause of the cancer-prone disease xeroderma pigmentosum. Here, we reconstitute the incision reaction of NER in Saccharomyces cerevisiae using purified protein factors. The Rad14 protein, the Rad4-Rad23 complex, the Rad2 nuclease, the Rad1-Rad10 nuclease, replication protein A, and the RNA polymerase II transcription factor TFI

The role of p28GANK in rat oval cells activation and proliferation.

BACKGROUND: Human gankyrin gene product (p28GANK) is a novel oncogenic protein ubiquitously overexpressed in hepatocellular carcinoma and also plays a role in cell cycle progression in normal hepatocytes and liver regeneration. However, little is known about the physiological role of p28GANK in the liver oval cell activation and proliferation. We investigated the possible involvement of p28GANK in oval cell-mediated liver regeneration and cell cycle progression. METHODS: We examined the different p28GANK expression in 2-acetylaminofuorene/partial heptectomy (2-AAF/PH) rats, as a model of oval

Mutagenesis and carcinogenesis in nucleotide excision repair-deficient XPA knock out mice.

Mice with a defect in the xeroderma pigmentosum group A (XPA) gene have a complete deficiency in nucleotide excision repair (NER). As such, these mice mimic the human XP phenotype in that they have a >1000-fold higher risk of developing UV-induced skin cancer. Besides being UV-sensitive, XPA(-/-) mice also develop internal tumors when they are exposed to chemical carcinogens. To investigate the effect of a total NER deficiency on the induction of gene mutations and tumor development, we crossed XPA(-/-) mice with transgenic lacZ/pUR288 mutation-indicator mice. The mice were treated with variou

Interstrain comparison of hepatic and renal microsomal carcinogen metabolism and liver S9-mediated mutagenicity in DA and Lewis rats phenotyped as poor and extensive metabolizers of debrisoquine.

Lewis (extensive metabolizers) and DA (poor metabolizers) rat strains show genetic polymorphism for the gene regulating debrisoquine 4-hydroxylation in a manner analogous to human drug polymorphism and show also a different toxicological response to aflatoxin B1. In order to investigate the underlying mechanism(s) of the different drug-metabolizing capacities, the in vitro metabolism and liver S9-mediated mutagenicity of several drugs and carcinogens were studied in female Lewis and DA rat strains, using untreated, 3-methylcholanthrene-treated, and phenobarbital-treated animals. S9-mediated mu

The SWI/SNF chromatin-remodeling factor stimulates repair by human excision nuclease in the mononucleosome core particle.

To investigate the role of chromatin remodeling in nucleotide excision repair, we prepared mononucleosomes with a 200-bp duplex containing an acetylaminofluorene-guanine (AAF-G) adduct at a single site. DNase I footprinting revealed a well-phased nucleosome structure with the AAF-G adduct near the center of twofold symmetry of the nucleosome core. This mononucleosome substrate was used to examine the effect of the SWI/SNF remodeling complex on the activity of human excision nuclease reconstituted from six purified excision repair factors. We found that the three repair factors implicated in da

Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA).

Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal stru

Characteristics of rat bone marrow cells differentiated into a liver cell lineage and dynamics of the transplanted cells in the injured liver.

BACKGROUND: Bone marrow cells (BMCs) have been shown to differentiate into a liver cell lineage, but little is known about their dynamics following transplantation. BMCs were cultured to investigate the expression of liver-specific genes in vitro and transplanted into in vivo liver-injury models to elucidate their dynamics in the liver. METHODS: The mRNA expression of various liver-specific genes in BMCs cocultured with hepatocytes was analyzed using reverse transcription-polymerase chain reaction. BMCs from transgenic rats expressing green fiuorescent protein were transplanted into the splee

Fibronectin and laminin induce expression of islet cell markers in hepatic oval cells in culture.

Hepatic oval cells (OC) are considered to be facultative liver stem cells and, because they may undergo differentiation into a variety of cell lineages, they might have the potential to be used in cellular therapy. Signals delivered by extracellular matrix (ECM) proteins take part in cellular differentiation in cooperation with signals from growth factors; indeed, some ECM proteins, such as laminin (LAM) and fibronectin (FN), have been shown to contribute to beta-cell differentiation and islet development, respectively. Since no previous studies have investigated the effect of ECM proteins on

Prospero-related homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from "oval cells".

The aim of this study was to analyse the changes of Prospero-related homeobox 1 (Prox1) gene expression in rat liver under different experimental conditions of liver injury, regeneration and acute phase reaction, and to correlate it with that of markers for hepatoblasts, hepatocytes, cholangiocytes and oval cells. Gene expression was studied at RNA level by RT-PCR, and at protein level by immunohistochemistry. At embryonal stage of rat liver development (embryonal days (ED) 14-16) hepatoblasts were found to be Prox1(+)/Cytokeratin (CK) 19(+) and alpha-fetoprotein (AFP)(+), at this stage Prox1(

15th Report on Carcinogens.

BACKGROUND: The Report on Carcinogens (RoC) is a congressionally mandated, science-based public health document that the National Toxicology … ew methods and established criteria. The listed substances include the following. A: Acetaldehyde; 2-Acetylaminofluorene; Acrylamide; Acrylonitrile; Adriamycin; Aflatoxins; Alcoholic Beverage Consumption; 2-Aminoanthraquinone; o-Aminoazotoluene; 4-Aminobiphenyl; 1-Amino-2,4-dibromoanthraquinone; 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (see Heterocyclic Amines [Sel …

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-

Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy and mode of action.

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be

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… Rutman RJ Cantarow A Paschkis KE Studies in 2-acetylaminofluorene carcinogenesis. I. The intracellular distribution of nucleic acids and protein in rat liver . Cancer Res 1954 ; 14 : 111 - 4 . 13126944 6. …

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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