INABILITY OF GALACTOSIDE-SPECIFIC MISTLETOE LECTIN TO INHIBIT N-METHYL-N-NITROSOUREA-INDUCED TUMOR-DEVELOPMENT IN THE URINARY-BLADDER OF RATS AND TO MEDIATE A LOCAL CELLULAR IMMUNE-RESPONSE AFTER LONG-TERM ADMINISTRATION

Extracts from mistletoe (Viscum album L.) are assumed to exert an anti neoplastic activity through their toxicity at high doses or by immunom odulation by nanogram quantities of a lectin. They are used as an unco nventional therapy modality in the management of a wide range of cance r diseases, although no anticancer potential has yet been demonstrated . This prompted us to study the effect of galactoside-specific lectin (VAA) - a major protein constituent of mistletoe with immunomodulatory properties - on chemically induced tumor development in the urinary b ladder of rats and on the local cellular immune response after long-te rm administration. To induce urothelial neoplasms N-methyl-N-nitrosour ea (MNU) was administered in a single intravesical dose (7.5 mg/kg bod y weight). Highly purified VAA was given subcutaneously at its immunom odulatory dose (1 ng/kg body weight) twice a week over the total exper imental period of 15 months, The incidences of epithelial bladder tumo rs were 25.0% following administration of MNU alone and 22.9% in the r ats additionally receiving VAA, which proved not to be significantly d ifferent (P = 0.81). Quantitative immunohistochemistry analyzing a pan el of immune cell types, including T lymphocytes, T helper/inducer cel ls (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for int erleukin-2 receptor (CD25), B lymphocytes and plasma cells, macrophage s, natural killer cells, granulocytes and all leukocytes expressing th e leukocyte common antigen (CD45), yielded no evidence for the ability of VAA to stimulate a substantial cellular immunological reaction in the wall of the normal urinary bladder or during urothelial carcinogen esis. In conclusion, the current experimental findings provide no supp ort at all that the galactoside-specific mistletoe lectin is capable o f inhibiting chemically induced bladder carcinogenesis and triggering a local cellular immune response after prolonged application. It thus seems highly improbable that commercial mistletoe preparations or VAA will be effective in the management of human bladder cancer by a cell- mediated immunological mechanism.