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Construction of a pumpless gravity-driven vascularized Skin-on-a-Chip for the study of hepatocytotoxicity in percutaneous exposure to exogenous chemicals.
Biomed Microdevices
September 2024
Department of Health Toxicology, College of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
Article Synopsis
- Existing Skin-on-a-Chip (SoC) technology faces limitations due to complex structures and the need for multiple devices, hindering the assessment of harmful chemicals that impact liver health after skin contact.
- A new gravity-driven SoC was developed, featuring three layers of cell chambers (human skin, blood vessel cells, and liver cells) that allows for effective study of liver toxicity from exogenous chemicals, with validation through specific parameters.
- This SoC accurately mimics the way chemicals are absorbed through the skin, processed in the bloodstream, and affect the liver, offering a potential substitute for animal testing in evaluating the safety of skin-penetrating chemicals.
Acetylation of putative arylamine and alkylaniline carcinogens in immortalized human fibroblasts transfected with rapid and slow acetylator N-acetyltransferase 2 haplotypes.
Arch Toxicol
January 2021
Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
Exposure to alkylanilines found in tobacco smoke and indoor air is associated with risk of bladder cancer. Genetic factors significantly influence the metabolism of arylamine carcinogens and the toxicological outcomes that result from exposure. We utilized nucleotide excision repair (NER)-deficient immortalized human fibroblasts to examine the effects of human N-acetyltransferase 1 (NAT1), CYP1A2, and common rapid (NAT2*4) and slow (NAT2*5B or NAT2*7B) acetylator human N-acetyltransferase 2 (NAT2) haplotypes on environmental arylamine and alkylaniline metabolism.
View Article and Find Full Text PDFSwitch-on effect on conformation-specific arylamine-DNA adduct by cyclometalated Ir(III) complexes.
J Biol Inorg Chem
March 2020
Advanced Materials Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600 020, India.
Arylamines are known to form covalent-DNA adducts upon metabolic activation. These covalent adducts adopt different conformational attributes, viz., major groove (B), stacked (S), and minor groove (W), and lead to different types of mutations.
View Article and Find Full Text PDFEffect of 2-acetylaminofluorene and its genotoxic metabolites on DNA adduct formation and DNA damage in 3D reconstructed human skin tissue models.
Mutagenesis
April 2021
Procter & Gamble, Mason, OH, USA.
In vitro genotoxicity assays utilising human skin models are becoming important tools for the safety assessment of chemicals whose primary exposure is via the dermal route. In order to explore metabolic competency and inducibility of CYP450 activating enzymes, 3D reconstructed human skin tissues were topically treated with 2-acetylaminofluorene (2-AAF) and its genotoxic metabolites, N-hydroxy-2-acetylaminofluorene (N-OH-2-AAF) and N-hydroxy-2-aminofluorene (N-OH-2-AF), which primarily cause DNA damage by forming DNA adducts. 2-AAF did not increase DNA damage measured in the reconstructed skin micronucleus (RSMN) assay when administered in multiple applications at 24 h intervals but was detected in the skin comet assay in the presence of the DNA polymerase inhibitor aphidicolin (APC).
View Article and Find Full Text PDFToxicological evaluation of Oviductus ranae: Acute, sub-acute and genotoxicity studies in mice and rats.
J Ethnopharmacol
May 2017
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China; Engineering Research Center for Agricultural Resources and Comprehensive Utilization of Jilin Provence, Jilin Institute of Chemical Technology, Jilin 132022, China. Electronic address:
Ethnopharmacological Relevance: Oviductus ranae (OR) is a traditional animal-based Chinese medicine, which has been listed in the Chinese Pharmacopoeia since 1985 edition. Although its medicinal application has been widely acknowledged, there is little available information on its potential toxicity.
Aim Of The Study: The aim of this study was to investigate the acute, sub-acute, and genetic toxicities of OR.
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