Transfected lymphocyte extracts of patients with urological tumours: complement temperature-sensitive adenovirus mutants in vitro

Patients with renal or bladder cancers exhibit a unique association with adenovirus (Ad) infections. About 60% of them contain antibodies to Ad early antigens. Both in their tumour cells and peripheral blood lymphocytes (PBL) they have detectable early Ad antigens known to be involved in malignant cell transformation. Transfection of tumour cell extracts resulted in complementing temperature-sensitive (ts) Ad mutants at nonpermissive temperatures (39 degrees C) indicating that some cells of the tumour mass possess active functions for Ad. Only 4 to 18% of control subjects were positive in these tests. Here we studied whether lymphocytes might be involved in tumourigenesis by Ad. PBL extracts of patients were transfected into HEp-2 culture cells, which were subsequently superinfected with Ad-5 ts18 and ts19 mutants at 39 degrees C. Titration of virus yields indicated complementation in 76% of patients with renal and bladder cancers in contrast to 20% of control individuals. Complementing ability of lymphocytes which had been prestimulated with phytohaemagglutinin (PHA) approached that of tumour extracts. It means that both specimens contain advanced functions in contrast to resting lymphocytes. Lymphocytes are nonpermissive for latently carried Ad infections. Expression, possible transfer of early Ad gene products via frequent contacts with tissue cells can result in removal of tumour suppressor gene products from complexes regulating cell cycle negatively. Further interaction with hormone-sensitive protooncogenes explains tissue, age and gender specificity of urological malignancies. These phenomena suggest an important cofactorial role for Ad in kidney and bladder tumours.