Mouse legs were irradiated with a dose of 30 Gy. After 50 days, when the acute reaction had regressed to a steady state, they were retreated with either 30 Gy of X rays delivered in six fractions over 12 days, six exposures to hyperthermia for 45 min at 42.7°C, six doses of cis-DDP, or a combination of these agents. The maximum skin reactions and the skin reactions integrated over 50 days were determined. The maximum skin response was found when the previously irradiated skin was treated with a combination of X irradiation and hyperthermia. The addition of cis-DDP to this regimen did not result in a further enhancement of the skin reaction. When the second treatment was irradiation alone or cis-DDP alone, the severity of the skin reactions was similar. Injury from the initial radiation dose persisted so that the cytotoxic action of cis-DDP resulted in a level of subacute skin damage that was similar to a second course of X irradiation.

Areas of skin approximately 1.5 cm in diameter on the legs of mice were made hyperthermic (30 min at 42.7°C) by exposure to an ultrasound beam (780 kHz), a single dose of X irradiation (2000 rad), or a combination of these treatments. After 35 days, when the acute reaction had reached a steady state, the same tissue was given a second treatment by either hyperthermia, irradiation, or a combination of hyperthermia and irradiation. When the first treatment was irradiation and the second treatment was either irradiation or a combination of hyperthermia and irradiation, the acute skin reactions were similar to those of skin not previously irradiated, indicating a large proportion of recovery from the first irradiation. When irradiation was the first treatment, a comparison of second treatments by hyperthermia plus irradiation with irradiation alone showed a thermal enhancement of 1.45. When the first treatment was hyperthermia plus irradiation, a comparison of second treatments by hyperthermia plus irradiation with irradiation also showed an enhancement factor of 1.45 for the combined treatment.

The influence of a chronic environmental stress on the incidence of radiation-induced tumors, lens opacities, and survival times was determined. Female CFN rats were exposed to whole-body irradiation with either 300 rad of fission neutrons, 600 rad of 250 kV X rays, or sham irradiation. Within each irradiated group, rats were assigned to one of four environments: exposure to 25°C until irradiated and immediately returned to (1) a 25°C or (2) a 2°C environment for duration of life; acclimation to a 2°C environment for 40 days, irradiated, then returned to (3) a 2°C or (4) a 25°C environment. Postirradiation exposure to the 2°C compared to the 25°C environment reduced tumor incidence in the X- and neutron-irradiated groups, but reduced incidence of lens opacities only in the neutron-irradiated group. A 2°C environment before and after irradiation produced similar results. Return of the 2°C acclimated rats to a 25°C environment increased incidence of tumors and lens opacities in the X-ray group, but reduced incidence of both in the neutron-irradiated rats. Chronic exposure to 2°C reduced the tumor incidence of nonirradiated rats but did not change the incidence of lens opacities. Median life expectancy was reduced by exposure to the 2°C environment. The data are consistent with the hypothesis that a chronic environmental stress initiated immediately after a carcinogen, in this study X or neutron radiation, may inhibit the malignant transformation. In view of other published data the stress-induced increase in metabolic rate may be an important factor in the inhibition.