Analyses of Oxidative DNA Damage and Its Repair Activity in the Livers of 3′‐Methyl‐4‐dimethylaminoazobenzene‐treated Rodents

Hirano, Takeshi; Higashi, Ken; Sakai, Akinori; Tsurudome, Yosuke; Ootsuyama, Yuko; Kido, Rie; Kasai, Hiroshi

doi:10.1111/j.1349-7006.2000.tb00999.x

Cited by 25 publications

(15 citation statements)

References 24 publications

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“…4, we confirmed that mOGG1-32 contains these regions. It is noteworthy that our previous observations indicated that the 8-OH-Gua excision repair activity in mouse liver was increased by up to 1.6-fold by treatment with 3′-MeDAB, 7) whereas the relative intensity of the 38-kDa mOGG1 showed no significant difference between the carcinogen-treated and control groups (Fig. 3B-a).…”

Section: Discussionmentioning

confidence: 60%

Detection of a smaller, 32‐kDa 8‐oxoguanine DNA glycosylase 1 in 3′‐methyl‐4‐dimethylamino‐azobenzene‐treated mouse liver

et al. 2004

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We previously reported that 3′ ′ ′ ′-methyl-4-dimethylaminoazobenzene (3′ ′ ′ ′-MeDAB) increased the 8-hydroxyguanine (8-OH-Gua) content in nuclear DNA and the base excision repair activity in mouse liver. However, to understand the mechanism of 3′ ′ ′ ′-MeDAB carcinogenesis, a further investigation of the 8-OH-Gua repair systems was necessary. In this report, we examined the expression of the repair enzyme, 8-oxoguanine DNA glycosylase 1 (OGG1), in 3′ ′ ′ ′-MeDAB-treated mouse liver. We prepared four kinds of anti-peptide polyclonal antibodies raised against mouse OGG1 (mOGG1). The sequences used as epitopes were designed from positions located close to the N-terminus, the nuclear localization signal (NLS), and the regions containing mino azo dye compounds have been reported to cause hepatocellular tumorigenesis in rodents.1, 2) In particular, 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB) is highly hepatocarcinogenic.3) The tumorigenic mechanisms are complex, and are thought to include carcinogen-DNA adduct formation 4,5) and reactive oxygen species (ROS) generation. 6)To determine if an ROS was involved in the carcinogenic mechanism, we previously measured the 8-hydroxyguanine (8-OH-Gua) level in the hepatic DNA of 3′-MeDAB-treated mice, and found that it was increased by up to 3.6-fold in comparison with that of control mouse liver.7) The 8-OH-Gua base excision repair activity was also increased by up to 1.6-fold. 8-OH-Gua is a major type of oxidative DNA damage, 8) and is known to be pre-mutagenic because it causes point mutations, such as GC to TA, in nuclear DNA.9-11) Therefore, we concluded that ROS generation was, at least in part, involved in 3′-MeDAB carcinogenesis.The repair enzyme for 8-OH-Gua (8-oxoguanine DNA glycosylase 1, OGG1) has glycosylase and lyase activities. 12,13) In the case of human OGG1, several splicing isoforms were reported 14) and were classified into mitochondrial type and a nuclear type, according to their C-terminal amino acid sequences. Only type 1a OGG1 has a nuclear localization signal (NLS), and it is believed to play a major role in 8-OH-Gua repair.15) All isoforms have a mitochondrial targeting signal (MTS), and the type 2a OGG1 might play a major role in 8-OH-Gua repair in mitochondria.16) Recent reports have shown that loss of heterozygosity (LOH) at the human OGG1 (hOGG1) locus occurs in a number of cancers, such as renal clear cell cancers and primary non-small cell lung cancers, suggesting that OGG1 is a type of cancer prevention factor. 17,18) Hence, it is reasonable to expect that an alteration of the Ogg1 gene is involved in tumor formation.In the present study, to examine the effect of 3′-MeDAB on 8-OH-Gua repair systems, we analyzed the expression of mouse OGG1 (mOGG1) protein in the livers of mice fed a diet containing 0.06% 3′-MeDAB for 8 months. Materials and MethodsAnimal treatments and sampling. Twelve 3-week-old male ddY mice were purchased from Seac Yoshitomi, Ltd. (Fukuoka) and were fed a commercial diet (Clea, Tokyo) and tap water ad libitum. These mice...

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Section: Discussionmentioning

confidence: 60%

Detection of a smaller, 32‐kDa 8‐oxoguanine DNA glycosylase 1 in 3′‐methyl‐4‐dimethylamino‐azobenzene‐treated mouse liver

et al. 2004

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“…5,6) Experiments in both cultured cells and animals have supported this premise. [7][8][9][10][11] Therefore, analyses of oxidative DNA damage should be useful to understand in detail the mechanisms of carcinogenesis. Moreover, the genes for the human and mouse glycosylase-type repair enzymes for 8-OHGua (hOGG1 and mOGG1) have been cloned.…”

mentioning

confidence: 99%

“…[12][13][14] The corresponding proteins have also been analyzed to study the mechanisms of carcinogenesis and to assess the cancer risks of chemical substances or environmental factors. [7][8][9][10][11] Several recent reports have suggested a relationship between oxidative DNA damage and the apoptotic process, [15][16][17] although, to our knowledge, only a few studies have investigated the relationship between 8-OH-Gua and apoptosis. Apoptosis is a physiological process of programmed cell death, which is characterized by distinct morphological changes and internucleosomal DNA fragmentation.…”

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confidence: 99%

Detection of a mouse OGG1 fragment during caspase‐dependent apoptosis: Oxidative DNA damage and apoptosis

et al. 2004

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We investigated the expression of mouse 8-oxoguanine DNA glycosylase 1 (mOGG1) in mouse non-parenchymal hepatocytes (NCTC) during etoposide-or mitomycin C (MMC)-induced apoptosis. We observed mOGG1 fragmentation in apoptotic cells. The apoptosis accompanying the fragmentation of mOGG1 was caspase-dependent. The mOGG1 fragment existed in both the cytoplasm and nucleus of the etoposide-treated NCTC, indicating that the mOGG1 fragment could be transferred into the nucleus. In addition, 8-hydroxyguanine (8-OH-Gua, 7,8-dihydro-8-oxoguanine) accumulated in the DNA of NCTC treated with etoposide, suggesting that the mOGG1 fragment might not function as a normal repair enzyme in etoposide-treated NCTC. Although we have not clarified in detail the mechanism and the significance of the mOGG1 fragmentation, further study of the fragmentation of DNA repair enzymes might provide insights into the relationship between oxidative DNA damage and apoptosis. (Cancer Sci 2004; 95: 634-638) ells are damaged by a number of environmental stresses, such as ultraviolet radiation, X-rays, heat shock, and chemical agents. Some of the stresses generate reactive oxygen species (ROS), which are highly toxic to cell maintenance processes and survival. ROS are known to induce several types of oxidative DNA damage, including premutagenic lesions, such as thymine glycol, 1) 5-hydroxymethyluracil, 2) 2-hydroxyadenine, 3) and 8-hydroxyguanine (8-OH-Gua). 4)8-OH-Gua is thought to be responsible for carcinogenesis, because it induces GC to TA transversion-type point mutations in DNA in vitro. 5,6) Experiments in both cultured cells and animals have supported this premise.7-11) Therefore, analyses of oxidative DNA damage should be useful to understand in detail the mechanisms of carcinogenesis. Moreover, the genes for the human and mouse glycosylase-type repair enzymes for 8-OHGua (hOGG1 and mOGG1) have been cloned. [12][13][14] The corresponding proteins have also been analyzed to study the mechanisms of carcinogenesis and to assess the cancer risks of chemical substances or environmental factors. [7][8][9][10][11] Several recent reports have suggested a relationship between oxidative DNA damage and the apoptotic process, [15][16][17] although, to our knowledge, only a few studies have investigated the relationship between 8-OH-Gua and apoptosis. Apoptosis is a physiological process of programmed cell death, which is characterized by distinct morphological changes and internucleosomal DNA fragmentation. The DNA damage induced by various stresses, including ROS, activates p53, which is an important molecule for the induction of cell cycle arrest or apoptosis in order to prevent oncogenesis. [18][19][20][21] The anticancer activities of some cancer chemotherapeutic agents, such as etoposide, mitomycin C (MMC), and cisplatin, are due to the induction of apoptosis. [22][23][24] Among these agents, etoposide has a topoisomerase II inhibitory action that is responsible for inducing apoptosis, and it recently was shown to be a pro-oxidant. 24) In our p...

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“…Some of them, such as N-methyl-4-aminoazobenzene, N, N-dimethyl-4-aminoazobenzene, and 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), are hepato-carcinogenic. We previously analyzed the effects of 3'-MeDAB on 8-oxo-Gua repair systems in rodent livers, and reported that 3'-MeDAB increased 8-oxo-Gua generation and decreased OGG1 expression, possibly by cleaving the protein [22]. These results suggested that the liver carcinogenicity of 3'-MeDAB was due to an increase in 8-oxo-Gua generation via 3'-MeDABinduced downregulation of OGG1 expression.…”

Section: Aminoazo Dyes and 8-oxo-gua / Ogg1mentioning

confidence: 93%

“…The decrease in the 8-oxo-Gua repair activity seems to be a reasonable consequence of the lower 8-oxo-Gua levels. Since we speculated that OGG1 fragmentation was a key event for 3'-MeDAB-induced 8-oxo-Gua accumulation [22], we predicted that OGG1 fragmentation might be inhibited by ethanol intake, as in the inhibition of the increase in 8-oxo-Gua levels. However, 12% ethanol intake failed to inhibit the 3'-MeDAB-induced fragmentation of OGG1 (groups D, E, and F in Fig.…”

Section: Alcohol and 8-oxo-gua / Ogg1mentioning

confidence: 99%

Food Factors and Oxidative DNA Damage / DNA Repair Systems

Hirano¹,

Tamae²

2011

Selected Topics in DNA Repair

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Analyses of Oxidative DNA Damage and Its Repair Activity in the Livers of 3′‐Methyl‐4‐dimethylaminoazobenzene‐treated Rodents

Cited by 25 publications

References 24 publications

Detection of a smaller, 32‐kDa 8‐oxoguanine DNA glycosylase 1 in 3′‐methyl‐4‐dimethylamino‐azobenzene‐treated mouse liver

Detection of a smaller, 32‐kDa 8‐oxoguanine DNA glycosylase 1 in 3′‐methyl‐4‐dimethylamino‐azobenzene‐treated mouse liver

Detection of a mouse OGG1 fragment during caspase‐dependent apoptosis: Oxidative DNA damage and apoptosis

Food Factors and Oxidative DNA Damage / DNA Repair Systems

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