Cancer chemoprevention by aliphatic selenocyanates: effect of chain length on inhibition of mammary tumors and DMBA adducts.
The objective of this study was to examine the anticarcinogenic activity of a series of aliphatic selenocyanates with increasing length of the carbon side chain, CH3-(CH2)n-SeCN, in which n = 0, 2, 4 or 6. Their ability to prevent mammary cancer was evaluated during the initiation phase using the rat 7,12-dimethyl-benz[a]anthracene (DMBA) model. Each compound was added to the diet at a final concentration of 2 p.p.m. Se and was given from 2 weeks before to 1 week after DMBA administration. Analysis of the tumor data suggested the following order of chemopreventive potency for this series of aliphatic selenocyanates: heptyl approximately pentyl > propyl > methyl. Thus it appears that the length of the carbon side chain is a determinant in modulating the efficacy of these selenium homologs. In vivo results of total DMBA binding and adduct formation in the mammary cells showed a similar trend of progressive reductions following treatment by selenocyanates with increasing length of the alkyl side chain. These studies strongly indicate that aliphatic selenocyanates are effective blocking agents in the DMBA model and are capable of modulating events in the initiation phase of mammary carcinogenesis.
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263.
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D003485:Cyanates / Q000627:therapeutic use*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D016588:Anticarcinogenic Agents; D003485:Cyanates; D018736:DNA Adducts; D016566:Organoselenium Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA