title: Enhanced photoproduct repair: its role in the DNA damage-resistance phenotype of human malignant melanoma cells.
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 for 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.
authors: Department of Zoology, University of Cambridge, United Kingdom.
authors: D H
authors: DH
authors: Hatton
authors: D L
authors: DL
authors: Mitchell
authors: P T
authors: PT
authors: Strickland
authors: R T
authors: RT
authors: Johnson
mesh_terms: D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair; D004261:DNA Replication; D004351:Drug Resistance; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D004247:DNA; D002945:Cisplatin