Enhanced photoproduct repair: Its role in the DNA damage-resistance phenotype of human malignant melanoma cells

D. H. Hatton, D. L. Mitchell, Paul Timothy Strickland, R. T. Johnson

Research output: Contribution to journalArticle

Abstract

A fundamental issue in understanding melanoma is to seek the basis for the cellular resistance to DNA damaging agents, which is manifested in vivo as pronounced tumor resistance to therapeutic agents. The published consensus on melanoma has been that exaggerated postreplication recovery (PRR), rather than excision repair, underlies the unusual damage-resistance phenotype. We examined the resistance to the model DNA damaging agent, UV-C, of subclones derived from a human metastatic melanoma cell line. The clones essentially fall into two groups: one with normal and the other with enhanced resistance. We exploited this range to investigate the interrelationships between replication, transcription, and repair of DNA after UV irradiation. Subclones resistant to UV killing were indeed found to possess enhanced rates of PRR and were coresistant to cisplatin. However, we now report an overall elevation of photoproduct repair in both melanoma groups compared to nonmelanoma controls and conclude that this accounts fur the resistant melanoma phenotype, including that of enhanced PRR. Repair enhancement may explain chemoresistance, while loss of efficiency of certain functions, such as PRR, due to the intrinsic genetic lability of tumor cells, may generate the class of melanoma subclones exhibiting only normal resistance.

Original languageEnglish (US)
Pages (from-to)181-189
Number of pages9
JournalCancer Research
Volume55
Issue number1
StatePublished - 1995

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DNA Damage
Melanoma
Phenotype
DNA Repair
DNA
Cisplatin
Neoplasms
Clone Cells
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Enhanced photoproduct repair : Its role in the DNA damage-resistance phenotype of human malignant melanoma cells. / Hatton, D. H.; Mitchell, D. L.; Strickland, Paul Timothy; Johnson, R. T.

In: Cancer Research, Vol. 55, No. 1, 1995, p. 181-189.

Research output: Contribution to journalArticle

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