BIOMAT Database Logo BIOMAT Database Logo

Attenuation of acridine mutagen ICR-191--DNA interactions and DNA damage by the mutagen interceptor chlorophyllin. 2008

Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Department of Physics and Biophysics, University of Warmia and Mazury in Olsztyn, Oczapowskiego 4, 10-719 Olsztyn, Poland.

We have investigated the ability of chlorophyllin (CHL) to interact with acridine mutagen ICR-191 (2-methoxy-6-chloro-9-(3-(2-chloroethyl)aminopropylamino)acridine) and also its ability to decrease binding of ICR-191 to DNA in a simple three-component competition system: CHL-ICR-DNA. Our data indicate a strong association of ICR-191 with CHL, stronger even than the association of ICR-191 with DNA. Calculations based on the measured affinity data show that a two- to three-fold excess of CHL reduces by about two-fold the concentration of the mutagen-DNA complex. We also exposed human leukemic HL-60 cells to ICR-191 in the absence and presence of CHL and measured the mutagen-induced DNA damage. The extent of DNA damage was assessed by analysis of histone H2AX phosphorylation. While ICR-191 induced significant increase in expression of phosphorylated H2AX (gammaH2AX), particularly in DNA replicating cells, this increase was totally abolished in the cells treated with ICR-191 in the presence of CHL.

UI MeSH Term Description Entries
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009588 Nitrogen Mustard Compounds A group of alkylating agents derived from mustard gas, with the sulfur replaced by nitrogen. They were formerly used as toxicants and vesicants, but now function as antineoplastic agents. These compounds are also powerful mutagens, teratogens, immunosuppressants, and carcinogens. Compounds, Nitrogen Mustard,Mustard Compounds, Nitrogen
D002735 Chlorophyllides Products of the hydrolysis of chlorophylls in which the phytic acid side chain has been removed and the carboxylic acids saponified. Chlorophyllide
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000585 Aminacrine A highly fluorescent anti-infective dye used clinically as a topical antiseptic and experimentally as a mutagen, due to its interaction with DNA. It is also used as an intracellular pH indicator. 9-Aminoacridine,Acridinamine,Aminacrine Hydrochloride,Aminoacridine,Aminoacridine Hydrochloride,Aminopt,Mykocert,9 Aminoacridine,Hydrochloride, Aminacrine,Hydrochloride, Aminoacridine
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D016587 Antimutagenic Agents Agents that reduce the frequency or rate of spontaneous or induced mutations independently of the mechanism involved. Anti-Mutagenic Agent,Antimutagen,Antimutagenic Agent,Anti-Mutagenic Agents,Anti-Mutagenic Effect,Anti-Mutagenic Effects,Antimutagenic Effect,Antimutagenic Effects,Antimutagens,Agent, Anti-Mutagenic,Agent, Antimutagenic,Agents, Anti-Mutagenic,Agents, Antimutagenic,Anti Mutagenic Agent,Anti Mutagenic Agents,Anti Mutagenic Effect,Anti Mutagenic Effects,Effect, Anti-Mutagenic,Effect, Antimutagenic,Effects, Anti-Mutagenic,Effects, Antimutagenic
D046911 Macromolecular Substances Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure. Macromolecular Complexes,Macromolecular Compounds,Macromolecular Compounds and Complexes,Complexes, Macromolecular,Compounds, Macromolecular,Substances, Macromolecular

Related Publications

Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Specificity of base substitutions induced by the acridine mutagen ICR-191: mispairing by guanine N7 adducts as a mutagenic mechanism.
December 1991, Genetics,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
The "interceptor" properties of chlorophyllin measured within the three-component system: intercalator-DNA-chlorophyllin.
August 2006, Biophysical chemistry,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Variation of the frameshift activity of a mutagen (ICR-191) following nitrosation in human gastric juice.
January 1981, Cancer letters,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Studies on DNA repair in frog and human cells exposed to an acridine half-mustard (ICR 191) and to MNNG.
March 1978, Mutation research,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
[Acridine mutagen ICR-170 induced developmental suppression of ovary and vitelline gland in female Schistosoma japonicum].
January 1995, Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Effects of an acridine half-mustard (ICR 191) on growth and ploidy of frog cells in culture.
February 1978, Journal of cellular physiology,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Frameshift mutations induced by the acridine mustard ICR-191 in embryos and in the adult gill and hepatopancreas of rpsL transgenic zebrafish.
October 2005, Mutation research,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Interactions of newly synthesized platinum nanoparticles with ICR-191 and their potential application.
March 2019, Scientific reports,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Mutation induction in Haemophilus influenzae by ICR-191. II. Role of DNA replication and repair.
February 1981, Mutation research,
Monika Pietrzak, and H Dorota Halicka, and Zbigniew Wieczorek, and Jolanta Wieczorek, and Zbigniew Darzynkiewicz
Interactions of chlorophyllin with acridine orange, quinacrine mustard and doxorubicin analyzed by light absorption and fluorescence spectroscopy.
May 2003, Biophysical chemistry,
Copied contents to your clipboard!