Hyperthermia responses in cell lines with normal and deficient DNA repairs systems

Abstract

Earlier data showed that cultured cells are more hyperthermia sensitive in S phase of the cell cycle. In part this sensitivity may be related to the disruption of DNA repair/processing activity in S phase. It is well known that many components of DNA repair systems are in fact involved in DNA replication/processing. For this study we set out to evaluate a wide range of DNA repair mutants to determine their thermal responses compared to the wild-type cells. Mutants of nucleotide excision repair (NER), homologous recombination repair (HR) and nonhomologous endjoining (NHEJ) were studied. In all cases the mutants were more thermally sensitive than the wild-type counterparts. In addition, studies on thermal tolerance (TT) showed that mutants did not have a smaller TT response than the wild type thus ruling out TT as a cause in the increased sensitivity. Cell cycle analysis showed no significant difference amongst mutant and wild-type cell line pairs and thus effects of differing cell cycle distribution was also ruled out. It is speculated that it may be the involvement of the mutated pathways in DNA replication/progressing that make mutated cells more sensitive than the wild types.