Immunological Control of Polyoma Virus Oncogenesis in Mice

Adult CBA mice thymectomized, treated with antilymphocytic globulin (ALG) and inoculated with human leprosy organisms were accidentally infected with polyoma virus and all developed tumours. After cessation of ALG administration, some animals were given spleen cells from syngeneic donors immunized with polyoma virus; none developed tumours. Similar results were obtained in mice deliberately infected with polyoma virus but not with leprosy organisms. Passive transfer of antibody before but not after virus inoculation prevented tumour formation in immunosuppressed recipients. Virus infection in thymectomized, lethally irradiated and bone marrow reconstituted mice resulted in only a very low incidence of tumours. These results emphasize the role of immunological surveillance in preventing polyoma tumour formation under natural conditions

Non-irradiation-derived reactive oxygen species (ROS) and cancer: therapeutic implications

Owing to their chemical reactivity, radicals have cytocidal properties. Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalysed reactions. Although these developments are currently still in their infancy, they nevertheless deserve consideration. There are now numerous examples known of conventional anti-cancer drugs that may at least in part exert cytotoxicity by induction of radical formation. Some drugs, such as arsenic trioxide and 2-methoxy-estradiol, were shown to induce programmed cell death due to radical formation. Enzyme-catalysed radical formation has the advantage that cytotoxic products are produced continuously over an extended period of time in the vicinity of tumour cells. Up to now the enzymatic formation of toxic metabolites has nearly exclusively been investigated using bovine serum amine oxidase (BSAO), and spermine as substrate. The metabolites of this reaction, hydrogen peroxide and aldehydes are cytotoxic. The combination of BSAO and spermine is not only able to prevent tumour cell growth, but prevents also tumour growth, particularly well if the enzyme has been conjugated with a biocompatible gel. Since the tumour cells release substrates of BSAO, the administration of spermine is not required. Combination with cytotoxic drugs, and elevation of temperature improves the cytocidal effect of spermine metabolites. The fact that multidrug resistant cells are more sensitive to spermine metabolites than their wild type counterparts makes this new approach especially attractive, since the development of multidrug resistance is one of the major problems of conventional cancer therapy