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 carried out in three in vivo models of MNU-induced mammary carcinogenesis in rats: a) a newly developed model characterized by the rapid but time-dependent appearance of intraductal proliferations, ductal carcinoma 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 work indicated that a) triphenylselenonium was able to delay the progression of premalignant to malignant lesions; b) chronic exposure to triphenylselenonium was required to sustain its cancer inhibitory activity; and c) triphenylselenonium failed to induce regression of established mammary carcinomas or suppress the emergence of new tumors when it was given at the late stage of carcinogenesis. These findings highlight the importance of understanding the range of activity of a given chemopreventive agent in order to maximize the probability of a successful outcome in the design of any future intervention trial.
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Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14293, USA. cip@sc3101.med.buffalo.edu
Thompson
H J
HJ
Ganther
H E
HE
D000818:Animals; D018890:Chemoprevention; D004334:Drug Administration Schedule; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016566:Organoselenium Compounds; C092819:triphenylselenonium chloride; D008770:Methylnitrosourea