Abstract
In analyzing the response of quiescent (Q) cells in solid tumors, we have developed a combined method with a micronucleus (MN) assay and the identification of proliferating (P) cells by 5-bromo-2'-deoxyuridine (BrdU) and an anti-BrdU monoclonal antibody. Using this method, the responses of Q tumor cells as well as total tumor (P+Q) cells within murine solid tumors to various DNA-damaging treatments, including radiation therapy, were evaluated. Based on this evaluation, combining with tirapazamine, a well-known bioreductive agent, and/or heat treatment at mild temperatures was thought to be a promising modality for cancer therapy in terms of conventional anticancer treatment-resistant Q cell control. Recently, Our method for detecting the Q-cell response using P cell labeling with BrdU and the MN frequency assay was also shown to be applicable to an apoptosis detection assay. Meanwhile, our method for detecting the intratumor Q-cell response was also applicable toward high linear energy transfer radiation, including reactor neutrons. We are now investigating the impact of p53 status of the tumor cells constituting solid tumors on intratumor Q cell response to various anticancer treatments. In addition, using our method, a new neutron capture compound that has the potential to be distributed in neutron capture therapy-resistant intratumor Q cell populations is now under development.
