Hyperbaric Oxygen Effect on Experimental Tumor Growth

Since the demonstration that the response of biologic systems to ionizing radiations is highly dependent on the presence of oxygen, numerous investigators have undertaken the clinical application of this concept (1–7). In an attempt to maximize the increase in tissue oxygen tension, oxygen under hyperbaric pressure has generally been employed. It has occasionally been observed (8) that in patients receiving radiotherapy under hyperbaric conditions metastases have appeared to develop, of unusual size or with dramatic rapidity. This raises the question of whether hyperbaric oxygen increases the propensity for localized solid tumors to disseminate or for circulating cancer cells to become implanted and produce metastases. The present communication describes experimental laboratory studies which are directed toward this question. Materials and Methods Two transplantable murine tumors with well denned biologic characteristics were used. For a number of years the Cloudman S91 melanoma has been serially passed at the National Cancer Institute by subcutaneous or intramuscular implantation into CDBA(F1) mice. In our studies, the inocula were prepared as a mash in normal saline, using a cytosieve technic (9), with the dilutions as described referring to ratios of tumor volume to cold normal saline. CDBA(F1) mice were inoculated intramuscularly in the right thigh with 0/1 ml tumor suspensions and randomized after tumor transplantation. Laboratory chow and water were provided ad libitum, and the experimental groups were exposed daily (five times per week) for one month to 100 per cent oxygen at 3 atmospheres absolute pressure for thirty minutes. The compression and decompression times were five minutes each, and the control groups were placed in the hyperbaric chamber for an identical length of time with the chamber door left partially open. Tumor volumes were determined by summing the maximum perpendicular diameters and dividing by four to obtain the radius with calculation of the volume, using the formula V = 4/3 π r3. The pigmented lung metastases of autopsied mice were macroscopically counted by an observer uninformed as to whether or not the individual mice had been exposed to hyperbaric oxygen. It has been previously shown (10) that these metastases tend to occur subpleurally, making the identification of the lesions quite simple, as shown in Figure 1. The leukemia LI210 system is an extensively studied tumor initially isolated from a DBA mouse and serially carried in this strain. Previous investigations have shown the tumor to be transplantable with single cell inocula prepared either by dilution technic or with a micromanipulator (11). In the present experiments, DBA mice were inoculated with a nominal single leukemic cell (dilution technic) and then randomized into hyperbaric oxygen or control (air) groups.