8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis

Makoto Kunisada, Kunihiko Sakumi, Yohei Tominaga, Arief Budiyanto, Masato Ueda, Masamitsu Ichihashi, Yusaku Nakabeppu, Chikako Nishigori

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Abstract

8-Oxoguanine is one of the oxidative DNA damages that can result in stable mutations. The Ogg1 gene encodes the repair enzyme 8-oxoguanine-DNA glycosylase, which removes the oxidized base from DNA. In this study, we investigated the role of 8-oxoguanine in skin carcinogenesis induced by UVB irradiation using Ogg1 knockout mice (C57B1/6J background). We examined the effect of UVB irradiation on the formation of 8-oxoguanine in epidermal cells using immunostaining and found that the level of 8-oxoguanine in Ogg1 knockout mice 24 hours after UVB irradiation remained high compared with that in wild-type and heterozygous mice. To verify the effect of chronic UVB irradiation on 8-oxoguanine formations in epidermal cells, we irradiated wild-type, heterozygous, and Ogg1 knockout mice with UVB at a dose of 2.5 kJ/m2 thrice a week for 40 weeks. We found that the mean number of tumors in Ogg1 knockout mice was 3.71, which was significantly more than in wild-type and heterozygous mice, being 1.71 and 2.28, respectively. The rate of developing malignant tumors in Ogg1 knockout mice was also significantly higher (88.5%; squamous cell carcinomas, 73.1%; sarcomas, 15.4%) than in wild-type mice (50.0%; squamous cell carcinomas, 41.7%; sarcomas, 8.3%). Moreover, the age of onset of developing skin tumors in Ogg1 knockout mice was earlier than in the other types of mice. These results clearly indicate that oxidative DNA damage induced by sunlight plays an important role in the development of skin cancers.

Original languageEnglish
Pages (from-to)6006-6010
Number of pages5
JournalCancer Research
Volume65
Issue number14
DOIs
Publication statusPublished - Jul 15 2005

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Knockout Mice
Carcinogenesis
Skin
Sarcoma
DNA Damage
Squamous Cell Carcinoma
DNA Glycosylases
Neoplasms
Sunlight
Skin Neoplasms
Age of Onset
8-hydroxyguanine
Mutation
DNA
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis. / Kunisada, Makoto; Sakumi, Kunihiko; Tominaga, Yohei; Budiyanto, Arief; Ueda, Masato; Ichihashi, Masamitsu; Nakabeppu, Yusaku; Nishigori, Chikako.

In: Cancer Research, Vol. 65, No. 14, 15.07.2005, p. 6006-6010.

Research output: Contribution to journalArticle

Kunisada, Makoto ; Sakumi, Kunihiko ; Tominaga, Yohei ; Budiyanto, Arief ; Ueda, Masato ; Ichihashi, Masamitsu ; Nakabeppu, Yusaku ; Nishigori, Chikako. / 8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis. In: Cancer Research. 2005 ; Vol. 65, No. 14. pp. 6006-6010.
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abstract = "8-Oxoguanine is one of the oxidative DNA damages that can result in stable mutations. The Ogg1 gene encodes the repair enzyme 8-oxoguanine-DNA glycosylase, which removes the oxidized base from DNA. In this study, we investigated the role of 8-oxoguanine in skin carcinogenesis induced by UVB irradiation using Ogg1 knockout mice (C57B1/6J background). We examined the effect of UVB irradiation on the formation of 8-oxoguanine in epidermal cells using immunostaining and found that the level of 8-oxoguanine in Ogg1 knockout mice 24 hours after UVB irradiation remained high compared with that in wild-type and heterozygous mice. To verify the effect of chronic UVB irradiation on 8-oxoguanine formations in epidermal cells, we irradiated wild-type, heterozygous, and Ogg1 knockout mice with UVB at a dose of 2.5 kJ/m2 thrice a week for 40 weeks. We found that the mean number of tumors in Ogg1 knockout mice was 3.71, which was significantly more than in wild-type and heterozygous mice, being 1.71 and 2.28, respectively. The rate of developing malignant tumors in Ogg1 knockout mice was also significantly higher (88.5{\%}; squamous cell carcinomas, 73.1{\%}; sarcomas, 15.4{\%}) than in wild-type mice (50.0{\%}; squamous cell carcinomas, 41.7{\%}; sarcomas, 8.3{\%}). Moreover, the age of onset of developing skin tumors in Ogg1 knockout mice was earlier than in the other types of mice. These results clearly indicate that oxidative DNA damage induced by sunlight plays an important role in the development of skin cancers.",
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