Journal Article

Mechanisms underlying DNA damage resistance in a <i>Xiphophorus</i> melanoma cell line

Steven Moredock, Rodney S. Nairn, Dennis A. Johnston, Michelle Byrom, Ginger Heaton, Megan Lowery and David L. Mitchell

in Carcinogenesis

Volume 24, issue 12, pages 1967-1975
Published in print December 2003 | ISSN: 0143-3334
Published online December 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg160
Mechanisms underlying DNA damage resistance in a Xiphophorus melanoma cell line

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The Xiphophorus hybrid fish model is an important resource for investigating the genetics and molecular biology of melanoma. Consistent with studies using human melanoma cell lines, the Xiphophorus melanoma cell line PSM, survives the lethal effects of ultraviolet-B radiation (UV-B) radiation much better than a cell line derived from normal fish tissue. In contrast to human melanoma cells, which show enhanced nucleotide excision repair, we do not see any differences in the efficiencies of photoenzymatic or nucleotide excision repair in normal and melanoma cell lines. We do, however, observe a significantly reduced growth rate in the melanoma cell line compared with the normal cell line and considerably less effect of UV-B radiation on DNA synthesis. The data suggest that the UV resistance phenotype of PSM cells is due more to the rate of proliferation and increased ability to replicate on a damaged template rather than enhanced repair of DNA photoproducts as observed in human melanoma cells. The putative increase in lesion bypass by DNA polymerase could result in higher mutation frequencies and enhanced genetic lability in fish melanoma cells.

Keywords: CPD, cyclobutane pyrimidine dimers; HBSS, Hank's buffered saline solution; NER, nucleotide excision repair; (6–4)PD, pyrimidine(6–4) pyrimidone dimer; PER, photoenzymatic repair; PRL, photoreactivating light; PRR, post-replication repair; RIA, radioimmunoassay; TdR, thymidine deoxyribonucleoside; UV-B, ultraviolet-B radiation

Journal Article.  5609 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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