Anesthetic agents modify tissue proteinase inhibitor content and tumor behavior

Anesthetic agents may modify the tissue content of low molecular weight proteinase inhibitors (mol wt less than 50,000) and affect the colonization and proliferation of B16-F10 melanoma cells in lungs. Lungs of female mice exposed to halothane in oxygen had significantly greater low molecular weight proteinase inhibitor activity than those from unexposed female mice. The amount of activity in male mice similarly exposed did not differ from unexposed controls. Lungs of exposed female mice also had greater activity as compared with males similarly exposed. No differences occurred in identical experiments with ketamine. High-performance liquid chromatography revealed that the inhibitor in all groups of both sexes shared a major peak with a molecular weight similar to that of the trypsin inhibitor aprotinin. Female mice bearing B16-F10 melanoma cells and exposed to halothane in oxygen had significantly more small lung tumor nodules than tumor-bearing female mice injected with ketamine. However, the total number of nodules did not differ between the two groups. These observations support the hypothesis that stimulation of proteinase inhibitory activity by halothane in oxygen may be responsible for an inhibition of tumor cell proliferation, resulting in smaller tumor nodules and no effect on the incidence of colonization.