M1G
Encyclopedia
M1G is a heterocyclic compound
which is a by-product
of base excision repair
(BER) of a specific type of DNA adduct
called M1dG. The M1dG adduct in turn is formed by a condensation reaction
between guanosine
nucleotides in DNA and either malondialdehyde
or base propenal
. If not repaired, these adducts are mutagenic
and carcinogenic
.
Malondialdehyde is an end product of lipid peroxidation
while base propenal is a result of DNA peroxidation.
M1dG is the major endogenous DNA adduct in humans. M1dG adducts have been detected in cell DNA in liver
, leucocytes, pancreas
and breast
in concentrations of 1-120 per 108 nucleotides. 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 for oxidative stress
.
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....
which is a by-product
By-product
A by-product is a secondary product derived from a 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 considered waste....
of base excision repair
Base excision repair
In biochemistry and genetics, base excision repair is a cellular mechanism that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky...
(BER) of a specific type of DNA adduct
DNA adduct
In molecular genetics, a DNA adduct is a piece of DNA covalently bonded to a chemical. This process could be the start of a cancerous cell, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure and as such are themselves measured to reflect quantitatively,...
called M1dG. The M1dG adduct in turn is formed by a condensation reaction
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...
between guanosine
Guanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...
nucleotides in DNA and either malondialdehyde
Malondialdehyde
Malondialdehyde is the organic compound with the formula CH22. The structure of this species is more complex than this formula suggests. This reactive species occurs naturally and is a marker for oxidative stress.- Structure and synthesis :...
or base propenal
Acrolein
Acrolein is the simplest unsaturated aldehyde. It is produced widely but is most often immediately reacted with other products due to its instability and toxicity...
. If not repaired, these adducts are mutagenic
Mutagen
In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...
and carcinogenic
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
.
Malondialdehyde is an end product of lipid peroxidation
Lipid peroxidation
Lipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism...
while base propenal is a result of DNA peroxidation.
M1dG is the major endogenous DNA adduct in humans. M1dG adducts have been detected in cell DNA in liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, leucocytes, pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
and breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
in concentrations of 1-120 per 108 nucleotides. 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 for oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
.