Accumulation of the Oxidative Base Lesion 8-Hydroxyguanine in DNA of Tumor-Prone Mice Defective in Both the 
 Myh
 and 
 Ogg1
 DNA Glycosylases

Russo, Maria Teresa; Luca, Gabriele De; Degan, Paolo; Parlanti, Eleonora; Dogliotti, Eugenia; Barnes, Deborah E.; Lindahl, Tomas; Yang, Hanjing; Miller, Jeffrey H; Bignami, Margherita

doi:10.1158/0008-5472.can-04-0355

Cited by 149 publications

(104 citation statements)

References 20 publications

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“…The main pathway to remove 8-oxoGua from DNA is base excision repair (BER) initiated predominantly by OGG1 glycosylase. 50 The activity of this enzyme is regulated by the next enzyme of the BER pathway: abasic sites endonuclease (Apex1). We observed an iron-triggered increase in levels of Apex1 mRNA, which was particularly large following supplementation with the single high dose of iron.…”

Section: Discussionmentioning

confidence: 99%

Benefits and Risks of Iron Supplementation in Anemic Neonatal Pigs

Lipiński¹,

Starzyński²,

Canonne‐Hergaux³

et al. 2010

The American Journal of Pathology

126

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Iron deficiency is a common health problem. The most severe consequence of this disorder is iron deficiency anemia (IDA), which is considered the most common nutritional deficiency worldwide. Newborn piglets are an ideal model to explore the multifaceted etiology of IDA in mammals, as IDA is the most prevalent deficiency disorder throughout the early postnatal period in this species and frequently develops into a critical illness. Here, we report the very low expression of duodenal iron transporters in pigs during the first days of life. We postulate that this low expression level is why the iron demands of the piglet body are not met by iron absorption during this period. Interestingly, we found that a low level of duodenal divalent metal transporter 1 and ferroportin, two iron transporters located on the apical and basolateral membrane of duodenal absorptive enterocytes, respectively, correlates with abnormally high expression of hepcidin, despite the poor hepatic and overall iron status of these animals. Parenteral iron supplementation by a unique intramuscular administration of large amounts of iron dextran is current practice for the treatment of IDA in piglets. However, the potential toxicity of such supplemental iron implies the necessity for caution when applying this treatment. Here we demonstrate that a modified strategy for iron supplementation of newborn piglets with iron dextran improves the piglets' hematological status, attenuates the induction of hepcidin expression, and minimizes the toxicity of the administered iron. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

Benefits and Risks of Iron Supplementation in Anemic Neonatal Pigs

Lipiński¹,

Starzyński²,

Canonne‐Hergaux³

et al. 2010

The American Journal of Pathology

126

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“…MYH interacts with apurinic/apyrimidinic endonuclease (APE) and proliferatingcell nuclear antigen (PCNA); furthermore, this enzyme excises adenine among G:A, G:A and C:A mismatched by 8-oxo, and then resects 8-oxo for repair by 8-oxoguanine DNA glycosylase (OGG1) (13,14). Mutations in MYH are involved in the initiation and progression of pulmonary, ovarian and gastrointestinal cancers, lymphoma and various other tumor types (5)(6)(7)(8)(9)(10).…”

Section: Discussionmentioning

confidence: 99%

“…8-oxoguanine (8-oxoG), which is generated from oxidative attack on guanine, is the most common form of oxidative DNA damage and displays a strong mutagenicity (3,4). One important enzyme that combats oxidative damage is MYH, a homolog of the transglucokinase Mut Y, which functions during DNA base excision repair and plays a significant role in the occurrence and development of various tumor types (5)(6)(7)(8)(9)(10). Since early detection of ESCC is difficult, with diffusion and metastasis typically occurring before diagnosis, we sought to determine whether MYH serves as a molecular marker for this disease.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of the DNA repair enzyme MYH in esophageal squamous cell carcinoma

Shen

Chen

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. MYH is an important enzyme in combating DNA oxidative stress in the occurrence and development of various types of tumors. To investigate the correlation between expression of the DNA repair enzyme MYH in esophageal squamous cell carcinoma and 8-oxoguanine (8-oxoG) oxidative damage, as well as the clinical significance of altered MYH expression, tissues from 175 esophageal carcinoma cases were investigated in the present study. MYH expression and 8-oxoG oxidative damage in squamous cell carcinoma and adjacent normal tissue were assessed by immunohistochemistry and Western blotting. In 82.9% (145/175) of the cases, MYH protein expression in esophageal squamous cell carcinoma was lower than that of adjacent normal tissue (t=4.24, P<0.001). Additionally, 8-oxoG staining was higher in the tumors than in the normal tissue. Lower expression of MYH in esophageal squamous cell carcinoma was associated with depth of invasion, venous invasion, TNM stage and lymph node metastasis (P<0.05). In conclusion, a lower MYH expression level in esophageal cell carcinoma tissue was inversely associated with more severe 8-oxoG oxidative damage, suggesting that changes in MYH activity correspond to increased DNA damage in tumor cells. The use of MYH expression as a postoperative index for esophageal squamous cell carcinoma may guide the formulation of individualized chemotherapy for patients after surgery.

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“…However, Myh and Ogg1"double knockout" mice displayed a marked increase of lymphomas and lung and ovarian tumors. Myh Ϫ/Ϫ mice have been shown to accumulate 8-oxo-G at an increased rate in the liver when compared with wild-type mice, although no age-dependent accumulation was detected in brain, small intestine, spleen, or kidney (20).…”

Section: Introductionmentioning

confidence: 98%