|
Hydroxyl radical products
- T --> thymine glycol
- A --> 4,6 diamino-5 formamidopyrimidine
- G --> 2,6 diamino-4-hydroxy-5 formamidopyrimidine
- G --> 8 hydroxyguanine
- sugar ---> strand breaks
Alkylating agents
- Dimethylnitrosamine
- Diethylnitrosamine
- N-methyl-N-nitrosourea (MNU)
- N-ethyl-N-nitrosourea
- 1,2 dimethylhydrazine
- methyl methane sulfonate
- ethyl methane sulfonate (EMS)
|
- Ionizing radiation (such as gamma and X rays) damages DNA. About 35% of the damage is by direct ionization of components
of the DNA. The remainder arises through the action of active
oxygen species (OH radical, superoxide anion, hydrogen peroxide),
particularly hydroxyl radical.
- Active oxygen species are also created during metabolism of a
number of compounds and through the Fe(II)-catalyzed Fenton reaction.
A variety of products result from free radical attack on DNA.
The principle ones are listed in the table at left.
- UV-C radiation is adsorbed directly by DNA bases. The most frequent
alteration resulting from UV-C is dimerization of the rings of
adjacent thymines, forming thymine dimers.
- A variety of chemicals react directly with DNA. Alkylating agents are electrophiles that add methyl, ethyl and more complicated alkyl groups to nucleic acid bases. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in vivo becomes a highly reactive methylating agent. Electrophilic reactants can also be generated by cytochrome P450 oxidation of xenochemicals. These chemicals include benzo[a]pyrene, acetylaminofluorene and aflatoxin. Bulky adducts result. Nitrogen and sulfur mustards (used in chemical warfare) link bases on opposite DNA strands, creating cross-links.
- Some chemicals intercalate between base pairs.
|
