DNA adduct
Encyclopedia
In molecular genetics
, a DNA adduct is a piece of DNA
covalently bonded
to a (cancer-causing) 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, for comparison, the amount of carcinogen exposure to the subject organism, i.e. rats or other living animals. Under experimental conditions for study, such DNA adducts are induced by known carcinogen
s, of which commonly used is DMBA (7,12-dimethylbenz(a)anthracene
). For example, the term "DMBA-DNA adduct" in a scientific journal refers to a piece of DNA that has DMBA attached to it. The presence of such an adduct indicates prior exposure to a potential carcinogen, but does not by itself indicate the presence of cancer in the subject animal .
DNA adducts include:
By-products include:
(DNA repair happens naturally under normal circumstances), this can lead to carcinogenesis, the beginnings of cancer.
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
, a DNA adduct is a piece of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
covalently bonded
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
to a (cancer-causing) chemical. This process could be the start of a cancerous cell, or carcinogenesis
Carcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
. DNA adducts in scientific experiments are used as biomarkers of exposure and as such are themselves measured to reflect quantitatively, for comparison, the amount of carcinogen exposure to the subject organism, i.e. rats or other living animals. Under experimental conditions for study, such DNA adducts are induced by known carcinogen
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...
s, of which commonly used is DMBA (7,12-dimethylbenz(a)anthracene
7,12-Dimethylbenz(a)anthracene
7,12-Dimethylbenzanthracene is an immunosuppressor and a powerful organ-specific laboratory carcinogen. Also known as 7,12-dimethylbenz[α]anthracene or DMBA, this substance is widely used in many research laboratories studying cancer. DMBA serves as a tumor initiator by making necessary mutations...
). For example, the term "DMBA-DNA adduct" in a scientific journal refers to a piece of DNA that has DMBA attached to it. The presence of such an adduct indicates prior exposure to a potential carcinogen, but does not by itself indicate the presence of cancer in the subject animal .
Examples
Chemicals which form DNA adducts include:- acetaldehydeAcetaldehydeAcetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
, is a significant constituent of tobacco smoke - cisplatinCisplatinCisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
binds to DNA and causes crosslinking, leading to death of the cell - DMBA (7,12-dimethylbenz(a)anthracene7,12-Dimethylbenz(a)anthracene7,12-Dimethylbenzanthracene is an immunosuppressor and a powerful organ-specific laboratory carcinogen. Also known as 7,12-dimethylbenz[α]anthracene or DMBA, this substance is widely used in many research laboratories studying cancer. DMBA serves as a tumor initiator by making necessary mutations...
) - malondialdehydeMalondialdehydeMalondialdehyde 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 :...
, a naturally occurring product of lipid peroxidationLipid peroxidationLipid 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...
DNA adducts include:
- etheno-DNA adducts: 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) and 3,N(4)-etheno-2'-deoxycytidine (epsilondC)
By-products include:
- M1GM1GM1G is a heterocyclic compound which is a by-product of base excision repair 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...
, a by-product of base excision repair (BER) of a specific type of DNA adduct called M1dG.
DNA Damage
When a chemical binds to DNA, the DNA becomes damaged, and proper and complete replication cannot occur to make the normal intended cell. This could be the start of a mutation, or mutagenesis, and without proper DNA repairDNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
(DNA repair happens naturally under normal circumstances), this can lead to carcinogenesis, the beginnings of cancer.