Changes in the antitumour effect of some cytostatic agents applied under conditions of morphine-induced hyperthermia

The effect of the cytostatic agents bleomycetin, vincristine and methotrexate on the growth of the Lewis lung carcinoma was investigated under conditions of normothermia and morphine-induced hyperthermia. Morphine was administered 1, 3, 5, 7, 9 and 11 days after the tumour transplantation (in a single of 20 mg/kg), 75 min prior to the administration of bleomycetin (in a single dose of 2 mg/kg), vincristine (in a single dose of 0.3 mg/kg) and methotrexate (in a single dose of 5 mg/kg). The therapeutic effect was assessed on the 24th hour after the end of the treatment through determining the tumour growth inhibition. The administration of morphine to mice was found to be accompanied by the development of a hyperthermal reaction, with a maximum between the 90th and 120th min after the treatment, the change in the rectal temperature of the animals being of the order of 2.2 +/- 0.14 degrees C. Hyperthermia potentiates the effect of the antitumour antibiotic bleomycetin which, unlike bleomycin, does not manifest a threshold effect of interaction with the hyperthermia. Temperatures of the order of 40 degrees C are found to result in sensitization of the relatively resistant cells of the Lewis lung carcinoma to the antitumour effect of vincristine. Hyperthermia did not affect the activity of methotrexate. The analysis of the data obtained suggests that morphine-induced hyperthermia is a convenient model in mice for testing the behaviour of the cytostatic agents under conditions of increased temperature.