J. Cadet et al. : DNA Modifications Due to Oxidative Damage
287
4
CONCLUSION
This review clearly shows the complexity of the oxidation reactions of DNA.
There is still an important need for development of accurate and sensitive methods
of detection of oxidative base damage in cellular and tissue DNA. Non-invasive
methods are particularly relevant for epidemiological studies. Further
developments would involve both molecular biology techniques (polymerase
chain reaction) and effective analytical methods such as capillary electrophoresis
associated with the sensitive and versatile electrospray mass spectrometry detection
technique. Efforts are currently made to determine the biological role of oxidized
base damage. One major aspect deals with repair studies which have already shown
the major role played by glycosylase proteins in the enzymatic removal of
damaged bases [for recent papers and reviews, see [24-26]].
The mutagenic assessment of oxidized DNA bases is based on site specific
incorporation of a single modification in sequence defined oligonucleotides [27].
Then, the resulting oligonucleotides can either be used as templates for DNA
replication investigations or further elongated prior to incorporation in eukaryotic
cells for mutagenic evaluation [for a recent review, see [28]].
KEYWORDS
Oxidative DNA damage, mutagenesis, genetic database, cancer risk, DNA database,
toxicology, biological effect, hydroxyl radical, guanine, epidemiological study.
REFERENCES
[I]
Ames B.N., Gold L.S. "Endogenous mutagens and the cause of aging and cancer", Mutat.
Res., 250, 3-16 (1991).
[2]
Sies H., ed. Oxidative Stress, "Oxidants and Antioxidants", New York, Academic Press Inc.,
(1991 ).
[3]
Lindahl T. "Instability and decay of the primary structure of DNA", Nature, 362, 709-715
(1993).
[4]
Srinivasan S., GIauert H.P. "Formation of 5-hydroxymethyl-2'-deoxyuridine in hepatic DNA
of rats treated with gamma-irradiation, diethylnitrosamine, 2-acetylaminofluorene or the
peroxisome proliferator ciprofibrate", Carcinogenesis, 11, 2012-2024 (1990).
[5]
Shinenaga M.K., Gimeno C.L., Ames B.N. "Urinary 8-hydroxy-2'-deoxyguanosine as a
biological marker of in vivo oxidative DNA damage", Proc. Natl. A cad. Sci. USA,86,
9697-9701 (1989).
[6]
von Sonntag C. ed. "The Chemical Basis of Radiation Biology", London: Taylor Francis,
(1987).
[7]
Cadet 1., Vigny P. "The photochemistry of nucleic acids", In: Morrison H, ed. Bioorganic
Photochemistry, Vol. 1, New York: Wiley and Sons, 1-272 (1990).
[8]
Wagner J.R., van Lier J.E., Decarroz C., Berger M., Cadet J. "Photodynamic methods for oxy
radical-induced DNA damage", Methods Enzym, 186, 502-511 (1990).
[9]
Wagner J.R., van Lier J.E., Berger M., Cadet J. "Thymidine hydroperoxides: Structural
assignment, conformational features, and thermal decomposition in water", 1. Am. Chern.
Soc., 116, 2235-2242 (1994).
[10] Cadet J. "DNA damage caused by oxidation, deamination, ultraviolet radiation and
photoexcited psoralens", In: Hemminki K et aI, eds. DNA adducts: Identification and
biological significance, Lyon: International Agency for Research on Cancer, IARC
Scientific Publications, 125, 245-276 (1994).
287
4
CONCLUSION
This review clearly shows the complexity of the oxidation reactions of DNA.
There is still an important need for development of accurate and sensitive methods
of detection of oxidative base damage in cellular and tissue DNA. Non-invasive
methods are particularly relevant for epidemiological studies. Further
developments would involve both molecular biology techniques (polymerase
chain reaction) and effective analytical methods such as capillary electrophoresis
associated with the sensitive and versatile electrospray mass spectrometry detection
technique. Efforts are currently made to determine the biological role of oxidized
base damage. One major aspect deals with repair studies which have already shown
the major role played by glycosylase proteins in the enzymatic removal of
damaged bases [for recent papers and reviews, see [24-26]].
The mutagenic assessment of oxidized DNA bases is based on site specific
incorporation of a single modification in sequence defined oligonucleotides [27].
Then, the resulting oligonucleotides can either be used as templates for DNA
replication investigations or further elongated prior to incorporation in eukaryotic
cells for mutagenic evaluation [for a recent review, see [28]].
KEYWORDS
Oxidative DNA damage, mutagenesis, genetic database, cancer risk, DNA database,
toxicology, biological effect, hydroxyl radical, guanine, epidemiological study.
REFERENCES
[I]
Ames B.N., Gold L.S. "Endogenous mutagens and the cause of aging and cancer", Mutat.
Res., 250, 3-16 (1991).
[2]
Sies H., ed. Oxidative Stress, "Oxidants and Antioxidants", New York, Academic Press Inc.,
(1991 ).
[3]
Lindahl T. "Instability and decay of the primary structure of DNA", Nature, 362, 709-715
(1993).
[4]
Srinivasan S., GIauert H.P. "Formation of 5-hydroxymethyl-2'-deoxyuridine in hepatic DNA
of rats treated with gamma-irradiation, diethylnitrosamine, 2-acetylaminofluorene or the
peroxisome proliferator ciprofibrate", Carcinogenesis, 11, 2012-2024 (1990).
[5]
Shinenaga M.K., Gimeno C.L., Ames B.N. "Urinary 8-hydroxy-2'-deoxyguanosine as a
biological marker of in vivo oxidative DNA damage", Proc. Natl. A cad. Sci. USA,86,
9697-9701 (1989).
[6]
von Sonntag C. ed. "The Chemical Basis of Radiation Biology", London: Taylor Francis,
(1987).
[7]
Cadet 1., Vigny P. "The photochemistry of nucleic acids", In: Morrison H, ed. Bioorganic
Photochemistry, Vol. 1, New York: Wiley and Sons, 1-272 (1990).
[8]
Wagner J.R., van Lier J.E., Decarroz C., Berger M., Cadet J. "Photodynamic methods for oxy
radical-induced DNA damage", Methods Enzym, 186, 502-511 (1990).
[9]
Wagner J.R., van Lier J.E., Berger M., Cadet J. "Thymidine hydroperoxides: Structural
assignment, conformational features, and thermal decomposition in water", 1. Am. Chern.
Soc., 116, 2235-2242 (1994).
[10] Cadet J. "DNA damage caused by oxidation, deamination, ultraviolet radiation and
photoexcited psoralens", In: Hemminki K et aI, eds. DNA adducts: Identification and
biological significance, Lyon: International Agency for Research on Cancer, IARC
Scientific Publications, 125, 245-276 (1994).