ABSTRACT
Eukaryotic DNA in a chromosome is believed to be organized into clusters of replicons whose replication is regulated in some temporal order such that all replicons within a cluster simultaneously initiate synthesis, and the cluster must be completely synthesized before other adjacent clusters can be replicated. In order to maximize the potential benefits of hyperthermia in cancer therapy either alone or combined with radiation and/or drugs, it is important to understand the basic mechanisms of how heat kills cells. Direct strand breakage of parental DNA by hyperthermia immediately after heating has not been observed with either alkaline-sucrose gradients or alkaline elution. There are numerous studies showing that hyperthermia damages the chromatin structure in cells, although the basic subunit structure of chromatin, the nucleosome, remains unchanged. At 42.5°C or lower, a maximum degree of inhibition is observed in CHO cells with longer heating times, suggesting thermotolerance for inhibition of DNA synthesis, DNA inhibition continues to increase with longer heating times.
