Induction of oh8Gua glycosylase in rat kidneys by potassium bromate (KBrO3), a renal oxidative carcinogen

Lee, Yong Kyu; Choi, Jeong‐Yun; Park, Min-Kyung; Choi, Eun‐Mi; Kasai, Hiroshi; Chung, Myung‐Hee

doi:10.1016/s0921-8777(96)00038-9

Cited by 40 publications

(10 citation statements)

References 31 publications

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“…injection at a dose of 80 mg/kg were increased in a time‐ and dose‐dependent manner. ( 20 ) Also, a recent report showed that KBrO 3 exposure at a dose of 400 p.p.m. in drinking water for 52 weeks was able to induce an approximately fourfold increase in OGG1 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

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In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys of rats given potassium bromate

Umemura¹,

Kanki²,

Kuroiwa³

et al. 2006

Cancer Science

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To clarify the role of 8-OHdG formation as a starting point for carcinogenesis, we examined the dose-dependence and timecourse of changes of OGG1 mRNA expression, 8-OHdG levels and in vivo mutations in the kidneys of gpt delta rats given KBrO 3 in their drinking water for 13 weeks. There were no remarkable changes in OGG1 mRNA in spite of some increments being statistically significant. Increases of 8-OHdG occurred after 1 week at 500 p.p.m. and after 13 weeks at 250 p.p.m. Elevation of Spi -mutant frequency, suggestive of deletion mutations, occurred after 9 weeks at 500 p.p.m. In a two-stage experiment, F344 rats were given KBrO 3 for 13 weeks then, after a 2-week recovery, treated with 1% NTA in the diet for 39 weeks. The incidence and multiplicity of renal preneoplastic lesions in rats given KBrO 3 at 500 p.p.m. followed by NTA treatment were significantly higher than in rats treated with NTA alone. Results suggest that a certain period of time might be required for 8-OHdG to cause permanent mutations. The two-step experiment shows that cells exposed to the alteration of the intranuclear status by oxidative stress including 8-OHdG formation might be able to form tumors with appropriate promotion. (Cancer Sci 2006; 97: 829-835) O xidative DNA damage is caused by reactive oxygen species derived from various processes of cellular metabolism, especially metabolism of exogenous mutagens and carcinogens. 8-OHdG, a form of guanine oxidized at the C-8 position, is believed to be fairly stable and the most abundant oxidative lesion(1) among the many oxidized nucleosides known. It is established that 8-OHdG lesions are repaired mainly by the so-called GO system.(2) In this system: OGG1 DNA glycosylase and apurinic/apyrimidic lyase act to correct 8-OH-G:C pairs; (3) MYH glycosylase removes an A base mispaired with 8-OHdG; (4) and MTH 8-OH-dGTpase hydrolyzes 8-OH-dGTP in the nucleotide pool for prevention of its incorporation into DNA.(5) Thus, the existence of these three genes for repair of 8-OHdG in DNA points to 8-OHdG as a biologically deleterious base lesion. Induction of OGG1 mRNA expression and an increase of OGG1 activity following application of exogenous oxidative stimuli have been demonstrated. (6)(7)(8)(9) KBrO 3 , which induces renal cell tumors in F344 rats after oral administration at concentrations of 250 and 500 p.p.m, (10) has been classified as a genotoxic carcinogen based on positive mutagenicity in the Ames, (11) chromosome aberration, (12) and micronucleus (13) tests. Effective prevention of KBrO 3 clastogenicity by antioxidants, (14,15) and induction of 8-OHdG by KBrO 3 in vitro and in vivo strongly suggest that 8-OHdG plays a key role in KBrO 3 mutagenesis and carcinogenesis. (16 -19) KBrO 3 has therefore received much attention as a suitable agent for research into 8-OHdG-related carcinogenesis. With a single dose of KBrO 3 by i.p. injection, 8-OHdG glycosylase activity in the rat kidney is increased in association with 8-OHdG formation.(20) A recent study using OGG1-deficient gpt delta mice...

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Section: Discussionmentioning

confidence: 99%

“…injection, 8‐OHdG glycosylase activity in the rat kidney is increased in association with 8‐OHdG formation. ( 20 ) A recent study using OGG1‐ deficient gpt delta mice found high amounts of 8‐OHdG in the genome DNA and GC:TA transversion mutations following KBrO 3 exposure at a concentration of 2000 p.p.m. for 12 weeks.…”

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confidence: 99%

In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys of rats given potassium bromate

Umemura¹,

Kanki²,

Kuroiwa³

et al. 2006

Cancer Science

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“…Hypothetically, any 8-OHdG that is formed might be removed (47) by enzymes that specifically recognize 8-OHdG in DNA and catalyze either base excision repair or nucleotide excision repair (48,49). One of these repair enzymes, 8-hydroxyguanine glycosylase, has been shown to be induced six-fold in rat kidneys under conditions of oxidative stress (50). However, preliminary experiments in our laboratory found no effect of exposure to intense light on the relative incorporation of [methyl-3H]thymidine or [8-3H]deoxyguanosine into retinal DNA of either dark-reared or dim light-reared rats, and thus no evidence for the induction of accelerated repair of oxidative lesions.…”

Section: Discussionmentioning

confidence: 99%

Light-induced Damage in the Retina: Differential Effects of Dimethylthiourea on Photoreceptor Survival, Apoptosis and DNA Oxidation

et al. 1999

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In the rat, photoreceptor cell death from exposure to intense visible light can be prevented by prior treatment with antioxidants. In this study we subjected albino rats raised in dim cyclic light and rats made more susceptible to light damage by rearing in darkness to exposures of green light that led to similar losses of photoreceptor cells. Rhodopsin and photoreceptor DNA, indicators of the number of surviving photoreceptor cells, were determined at various times over a period of 14 days after light exposure. Fragmentation of DNA was determined over a similar time course by neutral and alkaline agarose gel electrophoresis. Apoptosis in retinal DNA was measured by quantitating the appearance of 180 base pair (bp) nucleosomal fragments. Oxidation of DNA was measured by electrochemical detection of the nucleoside 8-hydroxydeoxyguanosine (8-OHdG) after separation by high-performance chromatography. For albino rats reared in dim cyclic light, 24 h of intense light exposure resulted in the loss of 50% rhodopsin and photoreceptor cell DNA. In dark-reared rats, the losses were 40%, respectively, after only 3 h of intense light treatment. In both cases pretreatment with the antioxidant dimethylthiourea (DMTU) prevented rhodopsin and photoreceptor cell DNA loss. The kinetics of the light-induced apoptosis depended markedly on the rearing environment of the rats. The DNA ladders appeared within 12 h of the onset of intense light in the rats reared in dim cyclic light. In these rats the 180 bp fragment was at two-thirds of its maximum intensity immediately after 24 h of light exposure and reached the maximum 12 h later. Dimethylthiourea partially inhibited ladder formation in rats reared in dim cyclic light and delayed the time of appearance of the 180 bp maximum by 6 h. By contrast, in rats reared in darkness the 180 bp fragment was undetected immediately after 3 h of light exposure and reached its maximum 2 days later. Pretreatment with DMTU completely eliminated DNA ladders in these rats. Alkaline gel electrophoresis revealed a pattern of single-strand DNA breaks, with relatively high molecular weight fragments, 6 h after light exposure of dark-reared rats. Single-strand DNA breaks in cyclic light rats corresponded with the onset of apoptotic ladders, but peak values preceded by 12 h the peak of DNA ladder formation. The quantity of 8-OHdG in retinal DNA remained close to control values in all samples with the exception of a peak of twice the control value 18 h after light exposure in the dark-reared rats and a value 60% higher 16 days after exposure in cyclic light animals. Dimethylthiourea had no effect on the amount of oxidized purine in any of the samples. The differences between dark-reared rats and rats reared in dim cyclic light in the kinetics of DNA fragmentation and in their response to treatment with DMTU is consistent with previous observations of fundamental differences in retinal cell physiology in these animals. In dim light-reared rats, the pathway to apoptosis may be qualitatively different from the pa...

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“…The constitutive levels of tissue endogenous antioxidants are low in long-lived animals, most likely because their rate of mtROSp is lower than in short-lived ones (sections II.A and II.B). Endogenous antioxidants (98) and DNA repair enzymes (88) are transitorily induced, when needed, to come back again to low levels when the episodic increase in oxidative stress has been overcome (88). In this way, cells save much energy, which otherwise would be invested in the protein synthesis needed to continuously maintain high levels of antioxidants and DNA repair enzymes when they are not needed at such high levels.…”

Section: Fig 12mentioning

confidence: 99%

Updating the Mitochondrial Free Radical Theory of Aging: An Integrated View, Key Aspects, and Confounding Concepts

Barja

2013

Antioxidants & Redox Signaling

253

240

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An updated version of the mitochondrial free radical theory of aging (MFRTA) and longevity is reviewed. Key aspects of the theory are emphasized. Another main focus concerns common misconceptions that can mislead investigators from other specialties, even to wrongly discard the theory. Those different issues include (i) the main reactive oxygen species (ROS)-generating site in the respiratory chain in relation to aging and longevity: complex I; (ii) the close vicinity or even contact between that site and the mitochondrial DNA, in relation to the lack of local efficacy of antioxidants and to sub-cellular compartmentation; (iii) the relationship between mitochondrial ROS production and oxygen consumption; (iv) recent criticisms on the MFRTA; (v) the widespread assumption that ROS are simple "by-products" of the mitochondrial respiratory chain; (vi) the unnecessary postulation of "vicious cycle" hypotheses of mitochondrial ROS generation which are not central to the free radical theory of aging; and (vii) the role of DNA repair concerning endogenous versus exogenous damage. After considering the large body of data already available, two general characteristics responsible for the high maintenance degree of long-lived animals emerge: (i) a low generation rate of endogenous damage: and (ii) the possession of tissue macromolecules that are highly resistant to oxidative modification.

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Induction of oh8Gua glycosylase in rat kidneys by potassium bromate (KBrO3), a renal oxidative carcinogen

Cited by 40 publications

References 31 publications

In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys of rats given potassium bromate

In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys of rats given potassium bromate

Light-induced Damage in the Retina: Differential Effects of Dimethylthiourea on Photoreceptor Survival, Apoptosis and DNA Oxidation

Updating the Mitochondrial Free Radical Theory of Aging: An Integrated View, Key Aspects, and Confounding Concepts

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