Activity of triphenylselenonium chloride in mammary cancer prevention.
The present study was designed to evaluate the tolerance and cancer chemopreventive activity of triphenylselenonium chloride in female Sprague-Dawley rats. No information is available in the literature on the anticarcinogenic efficacy of a lipophilic cationic selenium compound as exemplified by the triphenylselenonium ion. A short-term preliminary study indicated that it was well tolerated via the dietary route. Supplementation at levels up to 200 p.p.m. Se did not produce any apparent adverse effect in the animals. In the dimethylbenzanthracene mammary cancer model, a level of 30 p.p.m. Se in the diet reduced the total tumor yield by approximately 70% when treatment was applied during either the initiation phase or the post-initiation phase. In the MNU mammary cancer model, the inhibitory response was expressed only during the post-initiation phase. These findings suggest that the triphenylselenonium ion may have multiple modes of action in suppressing the development of neoplasia. Tissue analysis confirmed that there was minimal accumulation of total selenium until the level of supplementation reached 100 p.p.m. Se or above. Our study therefore convincingly demonstrates that triphenylselenonium chloride fits the criteria of an effective and desirable anticancer agent with a distinct separation between the chemopreventive dose range and the toxic dose range.
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Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Thompson
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Ganther
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D009929:Organ Size / Q000187:drug effects; D016566:Organoselenium Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D016588:Anticarcinogenic Agents; D016566:Organoselenium Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea