Intestinal carcinogenicity screening of environmental pollutants using organoid-based cell transformation assay
Arch Toxicol. 2024 Apr 2. doi: 10.1007/s00204-024-03729-y. Online ahead of print.ABSTRACTThe high incidence of colorectal cancer (CRC) is closely associated with environmental pollutant exposure. To identify potential intestinal carcinogens, we developed a cell transformation assay (CTA) using mouse adult stem cell-derived intestinal organoids (mASC-IOs) and assessed the transformation potential on 14 representative chemicals, including Cd, iPb, Cr-VI, iAs-III, Zn, Cu, PFOS, BPA, MEHP, AOM, DMH, MNNG, aspirin, and metformin. We optimized the experimental protocol based on cytotoxicity, amplification, and colony formation o...
Source: Archives of Toxicology - April 2, 2024 Category: Toxicology Authors: Ziwei Wang Shen Chen Yuzhi Guo Rui Zhang Qi Zhang Xinhang Jiang Miao Li Yue Jiang Lizhu Ye Xiaoyu Guo Chuang Li Guangtong Zhang Daochuan Li Liping Chen Wen Chen Source Type: research
Female offspring of mice perinatally exposed to benzophenone-3 showed early subfertility linked to a poor oocyte stockpile
In conclusion, perinatal exposure to BP3 leads to a decline in the reproductive capacity of female mice in a continuous breeding protocol linked to oocyte depletion.PMID:38553590 | DOI:10.1007/s00204-024-03730-5 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Valentina Galliani Juli án Elías Abud Mar ía Laura Zenclussen Horacio Adolfo Rodr íguez Source Type: research
A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03721-6. Online ahead of print.ABSTRACTThe first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction. We modified and applied a PF framework from the general risk assessment literatu...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Jerry Achar Mark T D Cronin James W Firman Gunilla Öberg Source Type: research
Transforming toxins into treatments: the revolutionary role of α-amanitin in cancer therapy
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03727-0. Online ahead of print.ABSTRACTAmanita phalloides is the primary species responsible for fatal mushroom poisoning, as its main toxin, α-amanitin, irreversibly and potently inhibits eukaryotic RNA polymerase II (RNAP II), leading to cell death. There is no specific antidote for α-amanitin, which hinders its clinical application. However, with the advancement of precision medicine in oncology, including the development of antibody-drug conjugates (ADCs), the potential value of various toxic small molecules has been explored. These ADCs ingeniously combine the targe...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Deyuan Ning Jinfang Xue Xiran Lou Ruifei Shao Yu Liu Guobing Chen Source Type: research
Effects of the nerve agent VX on hiPSC-derived motor neurons
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03708-3. Online ahead of print.ABSTRACTPoisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans. To overcome this limitation, motor neurons (MN) of this study were differentiated from in-house feeder- a...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Catherine Schaefers Wolfgang Schmei ßer Harald John Franz Worek Theo Rein Simone Rothmiller Annette Schmidt Source Type: research
Female offspring of mice perinatally exposed to benzophenone-3 showed early subfertility linked to a poor oocyte stockpile
In conclusion, perinatal exposure to BP3 leads to a decline in the reproductive capacity of female mice in a continuous breeding protocol linked to oocyte depletion.PMID:38553590 | DOI:10.1007/s00204-024-03730-5 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Valentina Galliani Juli án Elías Abud Mar ía Laura Zenclussen Horacio Adolfo Rodr íguez Source Type: research
A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03721-6. Online ahead of print.ABSTRACTThe first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction. We modified and applied a PF framework from the general risk assessment literatu...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Jerry Achar Mark T D Cronin James W Firman Gunilla Öberg Source Type: research
Transforming toxins into treatments: the revolutionary role of α-amanitin in cancer therapy
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03727-0. Online ahead of print.ABSTRACTAmanita phalloides is the primary species responsible for fatal mushroom poisoning, as its main toxin, α-amanitin, irreversibly and potently inhibits eukaryotic RNA polymerase II (RNAP II), leading to cell death. There is no specific antidote for α-amanitin, which hinders its clinical application. However, with the advancement of precision medicine in oncology, including the development of antibody-drug conjugates (ADCs), the potential value of various toxic small molecules has been explored. These ADCs ingeniously combine the targe...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Deyuan Ning Jinfang Xue Xiran Lou Ruifei Shao Yu Liu Guobing Chen Source Type: research
Effects of the nerve agent VX on hiPSC-derived motor neurons
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03708-3. Online ahead of print.ABSTRACTPoisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans. To overcome this limitation, motor neurons (MN) of this study were differentiated from in-house feeder- a...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Catherine Schaefers Wolfgang Schmei ßer Harald John Franz Worek Theo Rein Simone Rothmiller Annette Schmidt Source Type: research
Female offspring of mice perinatally exposed to benzophenone-3 showed early subfertility linked to a poor oocyte stockpile
In conclusion, perinatal exposure to BP3 leads to a decline in the reproductive capacity of female mice in a continuous breeding protocol linked to oocyte depletion.PMID:38553590 | DOI:10.1007/s00204-024-03730-5 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Valentina Galliani Juli án Elías Abud Mar ía Laura Zenclussen Horacio Adolfo Rodr íguez Source Type: research
A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03721-6. Online ahead of print.ABSTRACTThe first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction. We modified and applied a PF framework from the general risk assessment literatu...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Jerry Achar Mark T D Cronin James W Firman Gunilla Öberg Source Type: research
Transforming toxins into treatments: the revolutionary role of α-amanitin in cancer therapy
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03727-0. Online ahead of print.ABSTRACTAmanita phalloides is the primary species responsible for fatal mushroom poisoning, as its main toxin, α-amanitin, irreversibly and potently inhibits eukaryotic RNA polymerase II (RNAP II), leading to cell death. There is no specific antidote for α-amanitin, which hinders its clinical application. However, with the advancement of precision medicine in oncology, including the development of antibody-drug conjugates (ADCs), the potential value of various toxic small molecules has been explored. These ADCs ingeniously combine the targe...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Deyuan Ning Jinfang Xue Xiran Lou Ruifei Shao Yu Liu Guobing Chen Source Type: research
Effects of the nerve agent VX on hiPSC-derived motor neurons
Arch Toxicol. 2024 Mar 30. doi: 10.1007/s00204-024-03708-3. Online ahead of print.ABSTRACTPoisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans. To overcome this limitation, motor neurons (MN) of this study were differentiated from in-house feeder- a...
Source: Archives of Toxicology - March 30, 2024 Category: Toxicology Authors: Catherine Schaefers Wolfgang Schmei ßer Harald John Franz Worek Theo Rein Simone Rothmiller Annette Schmidt Source Type: research
The thrombopoietin mimetic JNJ-26366821 reduces the late injury and accelerates the onset of liver recovery after acetaminophen-induced liver injury in mice
Arch Toxicol. 2024 Mar 29. doi: 10.1007/s00204-024-03725-2. Online ahead of print.ABSTRACTAcetaminophen (APAP)-induced hepatotoxicity is comprised of an injury and recovery phase. While pharmacological interventions, such as N-acetylcysteine (NAC) and 4-methylpyrazole (4-MP), prevent injury there are no therapeutics that promote recovery. JNJ-26366821 (TPOm) is a novel thrombopoietin mimetic peptide with no sequence homology to endogenous thrombopoietin (TPO). Endogenous thrombopoietin is produced by hepatocytes and the TPO receptor is present on liver sinusoidal endothelial cells in addition to megakaryocytes and platelet...
Source: Archives of Toxicology - March 29, 2024 Category: Toxicology Authors: Olamide B Adelusi Jephte Y Akakpo Gary Eichenbaum Ejaz Sadaff Anup Ramachandran Hartmut Jaeschke Source Type: research
The thrombopoietin mimetic JNJ-26366821 reduces the late injury and accelerates the onset of liver recovery after acetaminophen-induced liver injury in mice
Arch Toxicol. 2024 Mar 29. doi: 10.1007/s00204-024-03725-2. Online ahead of print.ABSTRACTAcetaminophen (APAP)-induced hepatotoxicity is comprised of an injury and recovery phase. While pharmacological interventions, such as N-acetylcysteine (NAC) and 4-methylpyrazole (4-MP), prevent injury there are no therapeutics that promote recovery. JNJ-26366821 (TPOm) is a novel thrombopoietin mimetic peptide with no sequence homology to endogenous thrombopoietin (TPO). Endogenous thrombopoietin is produced by hepatocytes and the TPO receptor is present on liver sinusoidal endothelial cells in addition to megakaryocytes and platelet...
Source: Archives of Toxicology - March 29, 2024 Category: Toxicology Authors: Olamide B Adelusi Jephte Y Akakpo Gary Eichenbaum Ejaz Sadaff Anup Ramachandran Hartmut Jaeschke Source Type: research
