CYTOSTASIS AND CANCER CHEMOPREVENTION - INVESTIGATING THE ACTION OF TRIPHENYLSELENONIUM CHLORIDE IN IN-VIVO MODELS OF MAMMARY CARCINOGENESIS

In this study, specific aspects of the cancer chemopreventive activity of triphenylselenonium chloride were investigated. The research was c arried out in three in vivo models of MNU-induced mammary carcinogenes is in rats: a) a newly developed model characterized by the rapid but time-dependent appearance of intraductal proliferations, ductal carcin oma in situ and adenocarcinomas; b) a conventional model which took 5 months for full expression of all palpable tumors; and c) a late stage model which used tumor-bearing rats as the target population. Our wor k indicated that a) triphenylselenonium was able to delay the progress ion of premalignant to malignant lesions; b) chronic exposure to triph enylselenonium was required to sustain its cancel inhibitory activity; and c) triphenylselenonium failed to induce regression of established mammary carcinomas or suppress the emergence of new tumors when it wa s given at the late stage of carcinogenesis. These findings highlight the importance of understanding the range of activity of a given chemo preventive agent in order to maximize the probability of a successful outcome in the design of any future intervention trial.