In situ end labelling of DNA to detect apoptotic cell death in a variety of human tumours.

The present studies illustrate clinical applications of in situ end labelling (ISEL) of DNA to detect apoptosis in a variety of human malignancies including myelodysplastic syndromes (MDS, n=10), non-Hodgkin's lymphoma (NHL, n=10), head and neck cancer (n = 3), breast cancer (n = 1) and cervical cancer (n = 1). These studies also describe a new in situ double labelling technique to detect apoptosis and proliferation (S-phase cells) simultaneously in the same section of plastic embedded tissue. In vivo intravenous infusions of thymidine analogues (i.e. bromodeoxyuridine (BrdU) and/or iododeoxyuridine (IUdR)) followed by their detection with a specific monoclonal antibody in a plastic embedded biopsy, combined with ISEL in the same section, facilitated simultaneous estimations of apoptosis and proliferation. The most salient finding of these studies was excessive apoptosis in MDS including the cells in S-phase as indicated by uniquely double labelled cells in their bone marrow biopsies. On the other hand, a very low degree of apoptosis was observed in NHL and other solid tumours. Moreover, the solid tumours exhibited definite compartments of apoptosis and proliferation. Further experiments are underway to confirm these findings in a larger study in order to design appropriate therapeutic modalities for these disorders.