The Genotoxic and Pro-Apoptotic Activities of Advanced Glycation End-Products (MAGE) Measured with Micronuclei Assay Are Inhibited by Their Low Molecular Mass Counterparts

An association between the cancer invasive activities of cells and their exposure to advanced glycation end-products (AGEs) was described early in some reports. An incubation of cells with BSA-AGE (bovine serum albumin-AGE), BSA-carboxymethyllysine and BSA-methylglyoxal (BSA-MG) resulted in a significant increase in DNA damage. We examined the genotoxic activity of new products synthesized under nonaqueous conditions. These were high molecular mass MAGEs (HMW-MAGEs) formed from protein and melibiose and low molecular mass MAGEs (LMW-MAGEs) obtained from the melibiose and N-α-acetyllysine and N-α-acetylarginine. We have observed by measuring of micronuclei in human lymphocytes in vitro that the studied HMW-MAGEs expressed the genotoxicity. The number of micronuclei (MN) in lymphocytes reached 40.22 ± 5.34 promille (MN/1000CBL), compared to 28.80 ± 6.50 MN/1000 CBL for the reference BSA-MG, whereas a control value was 20.66 ± 1.39 MN/1000CBL. However, the LMW-MAGE fractions did not induce micronuclei formation in the culture of lymphocytes and partially protected DNA against damage in the cells irradiated with X-ray. Human melanoma and all other studied cells, such as bronchial epithelial cells, lung cancer cells and colorectal cancer cells, are susceptible to the genotoxic effects of HMW-MAGEs. The LMW-MAGEs are not genotoxic, while they inhibit HMW-MAGE genotoxic activity. With regard to apoptosis, it is induced with the HMW-MAGE compounds, in the p53 independent way, whereas the low molecular mass product inhibits the apoptosis induction. Further investigations will potentially indicate beneficial apoptotic effect on cancer cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Genes - 12(2021), 5 vom: 13. Mai

Sprache:

Englisch

Beteiligte Personen:

Czech, Monika [VerfasserIn]
Konopacka, Maria [VerfasserIn]
Rogoliński, Jacek [VerfasserIn]
Maniakowski, Zbigniew [VerfasserIn]
Staniszewska, Magdalena [VerfasserIn]
Łaczmański, Łukasz [VerfasserIn]
Witkowska, Danuta [VerfasserIn]
Gamian, Andrzej [VerfasserIn]

Links:

Volltext

Themen:

94ZLA3W45F
9B1VBE526I
Advanced glycation
Advanced glycation end-products
Apoptosis
Arginine
Genotoxicity
Glycation End Products, Advanced
Glycation products
Journal Article
K3Z4F929H6
Lysine
MAGEs
Melibiose
Micronuclei assay
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 23.08.2021

Date Revised 23.08.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/genes12050729

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM326166203