Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms.

Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals--such as antioxidant scavengers and enzymes--and to repair DNA damage.

Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved.

Reactive oxygen species from endogenous and environmental sources induce oxidative damage to DNA, and hence pose an enormous threat to the genetic integrity of cells.

Active oxygen species in the nucleotide pool of the cell can produce 8-oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate), which can then be incorporated into cellular DNA. Human cells contain enzyme activity that hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing occurrence of mutations caused by misincorporation.

This oxidative DNA damage is restored by the base excision repair (BER) pathway that is conserved from bacteria to humans and is initiated by DNA glycosylases, which simply remove the aberrant base from the DNA backbone by hydrolyzing the N-glycosidic bond (monofunctional DNA glycosylase), or further catalyze the incision of a resulting abasic site (bifunctional DNA glycosylase).

Features

 free radicals and aging
 free radicals and cancer
 interaction between nitric oxide and p53

References

 Zhang Y, Chen F. Reactive oxygen species (ROS), troublemakers between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK). Cancer Res. 2004 Mar 15;64(6):1902-5. PMID: #15026320#

 Goodman JE, Hofseth LJ, Hussain SP, Harris CC. Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease. Environ Mol Mutagen. 2004;44(1):3-9. PMID: #15199542#

 Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA. The antioxidant conundrum in cancer. Cancer Res. 2003 Aug 1;63(15):4295-8. PMID: 12907593

 Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer. 2003 Apr;3(4):276-85. PMID: #12671666#