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

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17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)285-298
Number of pages14
JournalMutation Research - DNA Repair
Volume459
Issue number4
DOIs
Publication statusPublished - May 31 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Toxicology
  • Genetics

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    Ichikawa, M., Nakane, H., Marra, G., Corti, C., Jiricny, J., Fitch, M., Ford, J. M., Ikejima, M., Shimada, T., Yoshino, M., Takeuchi, S., Nakatsu, Y., & Tanaka, K. (2000). Decreased UV sensitivity, mismatch repair activity and abnormal cell cycle checkpoints in skin cancer cell lines derived from UVB-irradiated XPA-deficient mice. Mutation Research - DNA Repair, 459(4), 285-298. https://doi.org/10.1016/S0921-8777(00)00005-7