Comparison of Thermoradiosensitization in Two Human Melanoma Cell Lines and One Fibroblast Cell Line by Concurrent Mild Hyperthermia and Low-Dose-Rate Irradiation

Abstract

Two human melanoma cell lines, one radioresistant (SK-MEL-3) and one radiosensitive (HT-144), and a normal human fibroblast line (AG1522) were evaluated for thermoradiosensitization of low-dose-rate irradiation by concurrent mild hyperthermia (39-41 degrees C). None of the cell lines expressed chronic thermotolerance during heating at 39-41 degrees C. The SK-MEL-3 cells were the most heat sensitive, while AG1522 and HT-144 cells had the same sensitivity at 39 and 40 degrees C but HT-144 cells were more sensitive at 41 degrees C. All cell lines expressed thermal enhancement of radiosensitivity with heating during irradiation which increased with heating temperature. The SK-MEL-3 cells, which were the most resistant to radiation and demonstrated the greatest repair of sublethal damage (SLD) during low-dose-rate irradiation, had the greatest thermal enhancement of radiosensitivity, while the HT144 cells, which were the most sensitive and expressed little repair of SLD during low-dose-rate irradiation, had the smallest thermal enhancement of radiosensitivity. These data show that concurrent mild hyperthermia during low-dose-rate irradiation may be most efficacious in radiation-resistant tumor cells which express resistance through an enhanced capacity for repair of SLD.

Enhanced cytotoxicity in combination of low dose-rate irradiation with hyperthermia in vitro

“…Since most basic research in hyperthermia oncology has been performed on rodent cells (Hahn 1982, Hall 1994, it is important to evaluate the interaction between heat and LDRI in human cell lines because the heat dependent response of human cell lines is substantially different from that of rodent cell lines (Raaphorst and Azzam 1983, Hahn et al 1989, Raaphorst et al 1989, Roizin-Towle and Pirro 1991, Mackey et al 1992a, Armour et al 1993. Recent research studies have indicated that, in comparison with rodent cells, most human cells are more resistant to higher temperature >42"C (Hahn et al 1989, Raaphorst et al 1989, Roizin-Towle and Pirro 1991 but are more sensitive to lower temperature, long duration mild hyperthennia (Mackey et al 1992a, 1992b, Armour et al 1993.…”

“…Recent research studies have indicated that, in comparison with rodent cells, most human cells are more resistant to higher temperature >42"C (Hahn et al 1989, Raaphorst et al 1989, Roizin-Towle and Pirro 1991 but are more sensitive to lower temperature, long duration mild hyperthennia (Mackey et al 1992a, 1992b, Armour et al 1993. Mackey et al (1992aMackey et al ( , 1992b demonstrated that HeLa cells were more sensitive to mild hyperthermia than Chinese hamster ovary cells.…”

Long duration mild temperature hyperthermia and brachytherapy

“…When combined LDMH/LDR therapy was applied to several human cell lines with a variety of heat and radiation sensitivities, LDR sensitization was observed in all with the largest degree of sensitization occurring in the most radiation resistant cell type 17,18 . In these studies, it was also shown that the most resistant cell lines had a greater capacity for repair of sublethal radiation damage and thus inhibition of sublethal damage repair (SLDR) by LDMH-enhanced radiosensitization in such cells, thereby overcoming resistance.…”

Evaluation of cell survival, DNA double strand breaks, and DNA synthesis during concurrent camptothecin and X‐radiation treatments

“…At this time, cells were in an actively proliferating phase, as judged from growth curves [5] and flow-cytometric measurements [27]. Plateau-phase cultures were obtained by seeding the same number of cells, incubating them under identical conditions for 5 days, completely replacing the medium and then using them for experiments 3 days later [5,28].…”