Intraperitoneal administration of 6.5 mg of methylated DNA, O6-methylguanine concentration being 11.5% that of guanine, to 3 month-old noninbred male rats was followed by a 5-fold decrease in the activity of O6-alkylguanine-DNA alkyltransferase (AT) within the first hour. The said enzyme is responsible for DNA O6-alkylguanine repair and plays a key role in mutagenic, carcinogenic and cytostatic effects of some alkylating agents. Within 24 hours, AT activity returned to normal to be followed by a significant increase. A correlation between the degree of inhibition of AT activity and dose of methylated DNA was established. Untreated DNA did not produce an inhibitory effect.

Download full-text PDF

Source

Publication Analysis

Top Keywords

o6-alkylguanine-dna alkyltransferase
8
administration methylated
8
methylated dna
8
[inactivation o6-alkylguanine-dna
4
alkyltransferase liver
4
liver rats
4
rats administration
4
methylated dna]
4
dna] intraperitoneal
4
intraperitoneal administration
4

Similar Publications

The DNA Alkyltransferase Family of DNA Repair Proteins: Common Mechanisms, Diverse Functions.

Int J Mol Sci

December 2023

School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK.

DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O-alkylguanine and O-alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein. Alkyltransferases then directly and irreversibly transfer the alkyl group from the base to the active site cysteine residue.

View Article and Find Full Text PDF

Unraveling key interactions and the mechanism of demethylation during hAGT-mediated DNA repair simulations.

Front Mol Biosci

September 2022

Department of Chemistry, School of Natural Sciences, Shiv Nadar Institution of Eminence Delhi-NCR, Uttar Pradesh, India.

Alkylating agents pose the biggest threat to the genomic integrity of cells by damaging DNA bases through regular alkylation. Such damages are repaired by several automated types of machinery inside the cell. O6-alkylguanine-DNA alkyltransferase (AGT) is an enzyme that performs the direct repair of an alkylated guanine base by transferring the alkyl group to a cysteine residue.

View Article and Find Full Text PDF

The Potential of Antibody Technology and Silver Nanoparticles for Enhancing Photodynamic Therapy for Melanoma.

Biomedicines

September 2022

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, 55 Beit Street, Doornfontein, Johannesburg 2028, South Africa.

Melanoma is highly aggressive and is known to be efficient at resisting drug-induced apoptotic signals. Resection is currently the gold standard for melanoma management, but it only offers local control of the early stage of the disease. Metastatic melanoma is prone to recurrence, and has a poor prognosis and treatment response.

View Article and Find Full Text PDF

Cancer stem cells (CSCs) from colorectal cancer (CRC), characterized by CD133 expression, have been associated with 5-fluorouracile (5-FU) chemoresistance. DNA repair mechanisms, such as O6-alkylguanine DNA alkyltransferase (MGMT) and mismatch repair (MMR) systems, have also been correlated to 5-FU resistance in CRC. The aim of this study was to evaluate the modulation of CD133 and MGMT in MMRproficient and MMR-deficient CRC cells under 5-FU treatment and the effect of this drug in CSCs.

View Article and Find Full Text PDF

Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA.

View Article and Find Full Text PDF

Want 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!