Significance of the response of quiescent cell populations within solid tumors in cancer therapy.
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 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. Thus, 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.
Masunaga
Shin-Ichiro
S
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Noda, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan. smasuna@rri.kyoto-u.ac.jp
Ono
Koji
K
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D016754:Boron Neutron Capture Therapy; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D004249:DNA Damage; D006801:Humans; D007399:Interphase; D051379:Mice; D015162:Micronucleus Tests; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*
D001973:Bromodeoxyuridine