Genetic toxicology of oxygen

Joenje, Hans

doi:10.1016/0921-8734(89)90001-5

Cited by 187 publications

(74 citation statements)

References 119 publications

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“…The answer appears to be that the mammalian cell nucleus is a relatively poorly oxygenated compartment (Joenje, 1989, Lindahl, 1993. Thus the most likely mechanism for endogenous cyclopurinedeoxynucleoside formation would involve the diffusion of hydrogen peroxide (H 2 O 2 ) into the cell nucleus, where it reacts with metals such as iron or copper that are present in close association with duplex DNA (Henle et al, 1999) via the Fenton reaction.…”

Section: In View Of This How Can Cyclopurine-deoxynucleoside Lesionsmentioning

confidence: 99%

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

Brooks

2007

Neuroscience

112

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Patients with the genetic disease xeroderma pigmentosum (XP) lack the capacity to carry out a specific type of DNA repair process called nucleotide excision repair (NER). The NER pathway plays a critical role in the repair of DNA damage resulting from UV radiation. A subset of XP patients develop a profound neurodegenerative condition known as XP neurological disease. Robbins and colleagues (PNAS 75:1984(PNAS 75: -88, 1978 hypothesized that since UV light cannot reach into the human brain, XP neurological disease results from some form of endogenous DNA damage that is normally repaired by the NER pathway. In the absence of NER, the damage accumulates, causing neuronal death by blocking transcription. In this manuscript, I consider the evidence that a particular class of oxidative DNA lesions, the 8, 5'-cyclopurine-2'-deoxynucleosides, fulfills many of the criteria expected of neurodegenerative DNA lesions in XP. Specifically, these lesions are chemically stable, endogenous DNA lesions that are repaired by the NER pathway but not by any other known process, and strongly block transcription by RNA polymerase II in cells from XP patients. A similar set of criteria might be used to evaluate other candidate DNA lesions responsible for neurological diseases resulting from defects in other DNA repair mechanisms as well.

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Section: In View Of This How Can Cyclopurine-deoxynucleoside Lesionsmentioning

confidence: 99%

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

Brooks

2007

Neuroscience

112

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“…This result is unexpected. Studies in mammalian cells in culture have found that hyperoxia can inactivate many enzymes crucial to normal metabolic function (Gardner et al, 1994;Joenje, 1989). Functional consequences of such changes include protein misfolding, catalytic inactivation, the loss of protein functions and a reduction in the function of glycolysis and the tricarboxylic (TCA) acid cycle (Das et al, 2001;Schoonen et al, 1990;Yan et al, 1997;Yan and Sohal, 1998).…”

Section: Effects Of 100% O 2 On Metabolic Ratementioning

confidence: 99%

“…Hyperoxia toxicity is thought to be caused by an increased production of free radicals and hydrogen peroxide generation (Joenje, 1989;Paget et al, 1987). Among other effects, hyperoxia can disrupt metabolic pathways and reduce respiration rates (Gille and Joenje, 1992;Jamieson, 1989;Schoonen et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Metabolic function inDrosophila melanogasterin response to hypoxia and pure oxygen

Voorhies

2009

Journal of Experimental Biology

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SUMMARYThis study examined the metabolic response of Drosophila melanogaster exposed to O 2 concentrations ranging from 0 to 21% and at 100%. The metabolic rate of flies exposed to graded hypoxia remained nearly constant as O 2 tensions were reduced from normoxia to ~3 kPa. There was a rapid, approximately linear reduction in fly metabolic rate at P O2 s between 3 and 0.5 kPa. The reduction in metabolic rate was especially pronounced at P O2 levels <0.5 kPa, and at a P O2 of 0.1 kPa fly metabolic rate was reduced ~10-fold relative to normoxic levels. The metabolic rate of flies exposed to anoxia and then returned to normoxia recovered to pre-anoxic levels within 30 min with no apparent payment of a hypoxia-induced oxygen debt. Flies tolerated exposure to hypoxia and/or anoxia for 40 min with nearly 100% survival. Fly mortality increased rapidly after 2 h of anoxia and >16 h exposure was uniformly lethal. Flies exposed to pure O 2 for 24 h showed no apparent alteration of metabolic rate, even though such O 2 tensions should damage respiratory enzymes critical to mitochondria function. Within a few hours the metabolic rate of flies recovering from exposure to repeated short bouts of anoxia was the same as flies exposed to a single anoxia exposure.

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“…Oxygen free radicals have been implicated in a number of degenerative diseases including aging and cancer (1)(2)(3)(4). These reactive species arise through normal cellular processes, inflammatory events, ischemia, and xenobiotic metabolism (5,6).…”

mentioning

confidence: 99%

Tandem double CC-->TT mutations are produced by reactive oxygen species.

Reid

Loeb

1993

Proc. Natl. Acad. Sci. U.S.A.

134

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Oxidative damage to DNA is mutagenic and thus may play a role in carcinogenesis. Because of the large number of different DNA lesions formed by oxidative species, no genetic alteration so far identified is exclusively associated with oxygen damage. Tandem double CC --TT mutations are known to occur via UV damage to DNA and are thought to be a specific indicator of UV exposure. Using a sensitive reversion assay that can detect both single and double mutations within the same codon of the M13-encoded lacZa gene, we show that treatments that produce reactive oxygen species can also produce tandem double CC -k TT mutations. The frequency at which these mutations occur is less than that for single base mutations by a factor of approximately 30. The induction of these mutations is inhibited by treatment that scavenges hydroxyl radicals. This unique mutation provides a marker of oxygen free radical-induced mutagenesis in cells that are not exposed to UV-irradiation and an indicator for assessing the involvement of oxidative damage to DNA in aging and tumor progression.

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Genetic toxicology of oxygen

Cited by 187 publications

References 119 publications

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

The case for 8,5′-cyclopurine-2′-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum

Metabolic function inDrosophila melanogasterin response to hypoxia and pure oxygen

Tandem double CC-->TT mutations are produced by reactive oxygen species.

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