An enzyme-linked immunosorbent assay (BA-ELISA) involving use of biotin-labeled anti-rabbit IgG and avidin-labeled horseradish peroxidase was developed for the measurement of O6-methyl-2'-deoxyguanosine (O6-MedGuo). Up to 5 micrograms of methylated DNA was enzymatically hydrolyzed, and the extent of inhibition of binding of immobilized O6-MedGuo-bovine serum albumin to rabbit anti-O6-MedGuo was measured. Fifty percent inhibition of antigen-antibody binding was achieved with 2.5 pmole of of O6-MedGuo. Separation of O6-MedGuo from unmodified nucleosides by high-performance liquid chromatography (HPLC-BA-ELISA) allowed detection of 700 fmole O6-MedGuo in 1 mg of DNA. Among the tobacco-related carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent. In F344 rats it induces nasal cavity, lung and liver tumors. Four hours after a single IV injection of NNK to F344 rats (87 mg/kg body weight), O6-MedGuo was present in target organs (mumole O6-MedGuo/mole dGuo) (nasal mucosa, 219; lung, 13.2; and liver, 34.5) but was not detectable in nontarget organs. F344 rats receiving daily IP injections of NNK (40 mg/kg body weight) for 14 days were sacrificed 24 hr after the last injection. The levels of (O6-Medguo/dGuo) were 7.9 and 11.4 mumole/mole in the nasal mucosa and lung, respectively. In the liver no O6-MedGuo was detected, but 1050 mumole of 7-MeGua/mole Gua was measured by HPLC-fluorimetry. No DNA methylation was observed in the nasal mucosa or liver of F344 rats treated with the nicotine-derived carcinogen N'-nitrosonornicotine.(ABSTRACT TRUNCATED AT 250 WORDS)
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1568691 | PMC |
| http://dx.doi.org/10.1289/ehp.8562197 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetic Characteristics of the Rat Fibroblast Cell Line Rat-1.
Cells
December 2024
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH, University Hospital Aachen, D-52074 Aachen, Germany.
The Rat-1 cell line was established as a subclone of the parental rat fibroblastoid line F2408, derived from Fisher 344 rat embryos. Rat-1 cells are widely used in various research fields, especially in cancer biology, to study the effects of oncogenes on cell proliferation. They are also crucial for investigating signal transduction pathways and play a key role in drug testing and pharmacological studies due to their rapid proliferation.
View Article and Find Full Text PDFIntracavitary cisplatin-fibrin followed by irradiation improved tumor control compared to the single treatments in a mesothelioma rat model.
JTCVS Open
December 2024
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Objective: To test the safety and efficacy of combination treatment for pleural mesothelioma (PM) with intracavitary cisplatin-fibrin (cis-fib) plus hemithoracic irradiation (IR) applied after lung-sparing surgery in an orthotopic immunocompetent rat model.
Methods: We randomized male F344 rats into 5 groups: cis-fib (n = 9), 10 Gy IR (n = 6), 20 Gy IR (n = 9), cis-fib+10 Gy IR (n = 6), and cis-fib+20 Gy IR (n = 9). Subpleural tumor implantation was performed on day 0 with 1 million syngeneic rat mesothelioma cells (IL45-luciferase).
Preliminary evaluation of ex vivo and in vivo skin permeability of aromatic amines.
PLoS One
January 2025
Research Center for Chemical Information and Management, National Institute of Occupational Safety and Health, Kawasaki, Japan.
A potential link has been reported between skin exposure to aromatic amines, such as ortho-toluidine (OT) and 3,3'-dichloro-4,4'-diaminodiphenylmethane (MOCA), and bladder cancer cases observed in Japanese chemical factories. To evaluate this association, we explored the permeability of OT and MOCA through pig skin and investigated the subsequent changes in plasma and urine concentrations in rats following percutaneous exposure. Employing Yucatan micropig skin, we first executed a permeability test by affixing the skin to a diffusion cell and applying 14C-labeled OT or MOCA.
View Article and Find Full Text PDFDevelopmental Toxicity of Disinfection Byproducts in F344 Rats: Effects on Pregnancy Maintenance and Eye Development.
Birth Defects Res
January 2025
Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA.
Background: Epidemiological studies report associations of drinking water disinfection byproducts (DBPs) with adverse health outcomes, including birth defects. Here, we used a rat model susceptible to pregnancy loss (full-litter resorption; FLR) and eye malformations (anophthalmia, microphthalmia) to test 11 DBPs, including trihalomethanes, haloacetic acids (HAAs), and nitrogen-containing DBPs (N-DBPs).
Methods: Timed-pregnant F344 rats received gavage doses of chloroform, chlorodibromomethane, iodoform, chloroacetic acid, bromoacetic acid, dibromoacetic acid (DBA), diiodoacetic acid (DIA), trichloroacetic acid (TCA), dibromonitromethane, and iodoacetonitrile on gestation days (GD) 6-10.
A novel serous ovarian carcinoma model induced by DMBA: Results from OncoTherad® (MRB-CFI-1) immunotherapy preclinical testing.
Biomed Pharmacother
January 2025
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Aims: The term ovarian carcinoma (OC) refers to a heterogeneous collection of five distinct diseases known as histotypes. While histotype-specific treatment is still a clinical challenge in OC, well-characterized models are required for testing new therapeutic strategies. We employed OncoTherad® (MRB-CFI-1), an interferon (IFN-γ)-stimulating nano-immunotherapy mediated by Toll-like receptors (TLR) 2/4, in association or not with Erythropoietin (EPO) in a chemically-induced ovarian cancer model.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!