Decreased UV sensitivity, mismatch repair activity and abnormal cell cycle checkpoints in skin cancer cell lines derived from UVB-irradiated XPA-deficient mice

Minoru Ichikawa, Hironobu Nakane, Giancarlo Marra, Chantal Corti, Josef Jiricny, Maureen Fitch, James M. Ford, Miyoko Ikejima, Takashi Shimada, Masafumi Yoshino, Seiji Takeuchi, Yoshimichi Nakatsu, Kiyoji Tanaka

研究成果: Contribution to journalArticle査読

17 被引用数 (Scopus)

抄録

Xeroderma pigmentosum group A gene (XPA)-deficient mice are defective in nucleotide excision repair (NER) and are therefore highly sensitive to ultraviolet (UV)-induced skin carcinogenesis. We established cell lines from skin cancers of UVB-irradiated XPA-deficient mice to investigate the phenotypic changes occurring during skin carcinogenesis. As anticipated, the skin cancer cell lines were devoid of NER activity but were less sensitive to killing by UV-irradiation than the XPA(-/-) fibroblast cell line. The lines were also more resistant to 6-thioguanine (6-TG) than XPA(-/-) and XPA(+/+) fibroblasts, which was suggestive of a mismatch repair (MMR) defect. Indeed, in vitro mismatch binding and MMR activity were impaired in several of these cell lines. Moreover, these cell lines displayed cell cycle checkpoint derangements following UV-irradiation and 6-TG exposure. The above findings suggest that MMR downregulation may help cells escape killing by UVB, as was seen previously for methylating agents and cisplatin, and thus that MMR deficient clones are selected for during the tumorigenic transformation of XPA(-/-) cells. Copyright (C) 2000 Elsevier Science B.V.

本文言語英語
ページ(範囲)285-298
ページ数14
ジャーナルMutation Research - DNA Repair
459
4
DOI
出版ステータス出版済み - 5 31 2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 毒物学
  • 遺伝学

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