Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA

Kasai, Hiroshi; Nishimura, Susumu; Kurokawa, Yuji; Hayashi, Yuzo

doi:10.1093/carcin/8.12.1959

Cited by 336 publications

(121 citation statements)

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“…Interestingly, potassium bromate shares with iron compounds the ability to cause not only mesothlioma 28 but also renal cell carcinoma 39 presumably by oxidative stress. 40 For the homozygous deletion to occur, DNA doublestrand breaks (DSBs) should be present, either as DNA damage or endogenous mechanisms. The presence of DSBs in the genomic DNA during replication is expected to result in homozygous deletion.…”

Section: Discussionmentioning

confidence: 99%

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Akatsuka

Yamashita

et al. 2010

Laboratory Investigation

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In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by microarray. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2 0 -deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion.

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Section: Discussionmentioning

confidence: 99%

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Akatsuka

Yamashita

et al. 2010

Laboratory Investigation

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“…DNA hydrolysis and microfiltration of the resultant samples were subsequently conducted by the method of Helbock et al (1999). The levels of 8-OHdG were then determined by an adaptation of the HPLC-ECD method of Kasai et al (1987) as described elsewhere (Nakae et al, 1994a;Yoshiji et al, 1992). Peaks gained with electrochemical (for 8-OHdG) and UV (for dG) detectors were integrated with a background noise correction loaded on an integrator.…”

Section: Hplc-ecd Assay For Nuclear 8-ohdg Levelsmentioning

confidence: 99%

Age and Organ Dependent Spontaneous Generation of Nuclear 8-Hydroxydeoxyguanosine in Male Fischer 344 Rats

Nakae

Akai

Kishida

et al. 2000

Laboratory Investigation

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SUMMARY: 8-Hydroxydeoxyguanosine (8-OHdG) is a major oxidative DNA adduct playing roles in senescence, carcinogenesis and various disease processes. High-performance liquid chromatography with an electrochemical detection (HPLC-ECD) method has been widely used to assess organ levels of 8-OHdG, and a recently introduced immunohistochemical approach has made it possible to clarify intra-organ localization. In the present study, these methods were employed to reveal age-dependent changes in nuclear 8-OHdG within various tissues of male Fischer 344 rats between 18 fetal days and 104 weeks of age. 8-OHdG was detected in the nuclei of cerebellar small granule and small cortical cells, cerebral nerve cells, and choroid plexus epithelia of the brain and ependymal cells of the spinal cord; parenchymal cells in the anterior lobe of the pituitary and adrenal glands (mainly cortex); bronchial epithelium of the lung; intra-hepatic bile duct, pancreatic duct, glandular gastric and intestinal epithelial cells; renal tubular epithelial cells (mainly medulla); and spermatogonia and spermatocytes of the testis and seminal vesicle epithelia. The nuclear 8-OHdG levels were high (more than two lesions per 10 6 deoxyguanosines) from 7 days to 104 weeks of age in the brain, 3 to 6 weeks in the adrenal gland, 6 to 104 weeks in the lung, and 3 to 52 weeks in the testis. In the other organs, the nuclear 8-OHdG levels remained low throughout. These findings provide a basis for research dealing with oxidative stress by indicating organ-specific and age-but not aging-dependent changes in the localization of spontaneously generated nuclear 8-OHdG in intact rats. The immunohistochemical approach has advantages for assessing variation of 8-OHdG formation at the cellular level not accessible to the HPLC-ECD method. (Lab Invest 2000, 80:249-261).

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“…The formation of thymine glycol and thymidine glycol in vivo has been used as a possible assay for oxidative DNA damage [28,43]. Very recently, the formation of 8-hydroxydeoxyguanosine in DNA by oxygen radicals was reported [44][45][46][47][48][49].…”

Section: Oxidative Damage To Dna and Its Relationship To Cancer And Amentioning

confidence: 99%

Do mitochondrial DNA fragments promote cancer and aging?

Richter

1988

FEBS Letters

211

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Reactive oxygen species are important in carcinogenesis, diseases, and aging, probably through oxidative damage of DNA. Our understanding of this relationship at the molecular level is very sketchy. It has recently been found that in mitochondria oxidative DNA damage is particularly high and may not be repaired efficiently. I propose that oxidatively generated DNA fragments escape from mitochondria and become integrated into the nuclear genome. This may transform cells to a cancerous state. Time‐dependent nuclear accumulation of mitochondrial DNA fragments may progressively change the nuclear information content and thereby cause aging. This proposal can be tested experimentally.

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Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA

Cited by 336 publications

References 0 publications

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma

Age and Organ Dependent Spontaneous Generation of Nuclear 8-Hydroxydeoxyguanosine in Male Fischer 344 Rats

Do mitochondrial DNA fragments promote cancer and aging?

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