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M1G (pyrimido
,2-''a'' The comma is a punctuation mark that appears in several variants in different languages. Some typefaces render it as a small line, slightly curved or straight, but inclined from the vertical; others give it the appearance of a miniature fille ...
urin-10(''3H'')-one) is a
heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...
which is a
by-product A by-product or byproduct is a secondary product derived from a production process, manufacturing process or chemical reaction; it is not the primary product or service being produced. A by-product can be useful and marketable or it can be cons ...
of
base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...
(BER) of a specific type of
DNA adduct In molecular genetics, a DNA adduct is a segment of DNA bound to a Carcinogen, cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers ...
called M1dG. The M1dG adduct in turn is formed by a
condensation reaction In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a ...
between
guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosp ...
nucleotides in
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
and either
malondialdehyde Malondialdehyde belong to the class of β-dicarbonyls. A colorless solid, malondialdehyde is a highly reactive compound that occurs as the enol. It is a physiological metabolite, and a marker for oxidative stress. Structure and synthesis Malon ...
(propanedial) or
acrolein Acrolein (systematic name: propenal) is the simplest unsaturated aldehyde. It is a colorless liquid with a foul and acrid aroma. The smell of burnt fat (as when cooking oil is heated to its smoke point) is caused by glycerol in the burning fat ...
. If not repaired, these adducts are
mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...
ic and
carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
ic. Malondialdehyde is an end product of
lipid peroxidation Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz ...
while
acrolein Acrolein (systematic name: propenal) is the simplest unsaturated aldehyde. It is a colorless liquid with a foul and acrid aroma. The smell of burnt fat (as when cooking oil is heated to its smoke point) is caused by glycerol in the burning fat ...
is a result of DNA peroxidation. M1dG is the major
endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
DNA adduct in humans. M1dG adducts have been detected in cell DNA in
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
leucocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
,
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
and
breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...
in concentrations of 1-120 per 108
nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
. Detection and quantification of M1dG adducts in the body as measured by free M1G is a tool for detecting DNA damage that may lead to cancer. Free M1G is also
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
for
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
.


References


External links

* * {{MeshName, 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido(1,2-alpha)purin-10(3H)-one Biochemistry Carcinogenesis Purines