Differential Sensitivity of Three Sublines of the Rat Dunning Prostate Tumor System R3327 to Radiation and/or Local Tumor Hyperthermia

Abstract

To better understand the relationship of the growth characteristics of tumor tissues and their response to ionizing radiation alone and in combination with local tumor hyperthermia, we compared three different tumor sublines of the Dunning rat prostate carcinoma R3327. This report includes results obtained with the anaplastic AT1 subline (volume doubling time 5.2 days), the moderately differentiated mucin-secreting HI subline (volume doubling time about 9 days) and the well-differentiated, hormone-dependent H subline (volume doubling time about 17 days). The effects of single doses of photons (10 to 40 Gy) with and without local tumor hyperthermia (35 min immersion at 43.5 degrees C) were quantified by growth delay. The time to reach five times the volume at the time of treatment after 30 Gy alone was found to be 56.0, 134.9 and 184.0 days for the R3327-AT1, HI and H tumors, respectively. The R3327-H tumor was more radiosensitive than the AT1 or HI subline. Five of nine R3327-H tumors were controlled locally with a single dose of photons (40 Gy). Local tumor hyperthermia alone induced growth delay in both differentiated tumors, while the anaplastic tumor subline did not respond. Combined treatment modalities with heat applied directly after irradiation revealed isoeffective thermal enhancement ratios for 30 Gy which decreased from 1.59 for the AT1 tumor and 1.42 for the HI tumor to 1.23 in the well-differentiated subline R3327-H.

Relative Biological Effectiveness of Carbon Ions for Local Tumor Control of a Radioresistant Prostate Carcinoma in the Rat

“…Nevertheless, the degree of hypoxia is not sufficient to induce central necrosis, as is often seen in the more rapidly proliferating rodent tumors. Chronic hypoxia is one of the reasons why this syngeneic tumor subline exhibited a high radiation resistance, as documented in previous animal studies with various radiation modalities (46)(47)(48). This resistance is also known from cell experiments with X-rays, in which a values of 0.144 and 0.068 Gy À1 were measured for oxic and hypoxic conditions, respectively, leading to an oxygen enhancement ratio of 2.35 (49).…”

The Dunning model

“…The use of radiation in conjunction with localized hyperthermia has also been explored, as previously mentioned. Several groups have examined the synergistic effects of hyperthermia and radiation treatment, examined at several different dosages and treatment designs, and in several morphologically distinct Dunning tumors [61,62].…”

The importance of schedule in whole body thermochemotherapy

“…The importance of timing when radiation is combined with local-regional thermal therapy has been well documented [18][19][20][21]; however, the timing of chemotherapy drugs with thermal therapy has received less attention. A few studies do show that the timing of chemotherapy drugs with one another, and with heat, is critically important.…”