CHARACTERISTICS OF ANTITUMOR-ACTIVITY OF DIMETHOXYBENZOYL)-1-PIPERAZINYL]-2(1H)-QUINOLINONE (VESNARINONE) AGAINST A HUMAN ADENOID SQUAMOUS CARCINOMA-FORMING CELL-LINE GROWN IN ATHYMIC NUDE-MICE

The tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a m inor salivary gland, were treated with a differentiation-inducing agen t, vesnarinone, which was given per o.s, daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistoch emically, The vesnarinone treatment resulted in a significant suppress ion of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tum ors, but not in untreated controls, Tissue sections from vesnarinone-t reated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen Le(Y) or proliferating cell nuc lear antigen (PCNA) and with rabbit polyclonal antibody to p53, Antibo dy staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragme ntation patterns as revealed by 3'-OH nick-end labelling techniques, T issue sections from vesnarinone-treated TYS tumors showed positive rea ction with nick-end labelling and were extensively stained strongly by anti-Le(Y) MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-Le(Y) M Ab. Within Le(Y)-positive areas of tissue sections from the vesnarinon e-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all Le(Y) -positive cells showed such signs of apoptosis. Le(Y)-positive cells s howed consistent negative staining by anti-PCNA MAb and anti-p53 rabbi t serum. From these findings, it can be considered that vesnarinone ha s differentiation and apoptosis-inducing activity against TYS cells gr own in athymic nude mouse.