Radiosensitization of pulmonary metastases—I In vivo testing of hycanthone, insulin and razoxane

Abstract

After the removal of a primary Lewis lung tumor from the flank of C57 Black mice, the metastases occurring in the lungs were used to investigate drugs as possible radiosensitizers. The left mouse lung was X-irradiated: the right lung acted as a reference. As selected and justified in our earlier paper (1978), the response measured was the ratio of the summed diameters of metastases per gram lung wt, left/right. This “metastases-only” model resembles the commonest clinical problem, the presence of potentially lethal metastases after excision of the primary. With this “model”, there was no chemotherapeutic action of single doses of the drugs or adjuvant solutions used. Doses of 12–24 Gray (1200–2400 rad) of X-irradiation were given alone or after a single injection of a drug. Statistically significant ( p = < 0.05) radiosensitization of metastases was obtained using either 2mg/25g mouse of hycanthone methanesulfonate (an actinomycin D-like substance) or 56 milliunits (mU) of insulin. The latter reduced the mouse's blood sugar to about 30%. At these dose levels, “4-point” assays showed that the effect of 12 Gray of X-rays could be reproduced by 7 Gray plus hycanthone or 6.7 Gray plus insulin. Razoxane (ICRF 159) was also investigated, as single doses of 2.5–25 mg in 10% dimethylsulfoxide (DMSO) or 0.5% carboxymethylcellulose (CMC). In various experiments, it was given at 5 time intervals before X-irradiation. While it caused some decreases in the L/R ratio, these were never statistically significant nor was there any trend in the results. Hence, without ruling out the possibility of razoxane action under other circumstances, no radiosensitization was observed under our reported conditions.