The present study examined the
mammary cancer chemopreventive activity of
Se-methylselenocysteine,
Se-propylselenocysteine and
Se-allylselenocysteine in the rat
methylnitrosourea (MNU) model. Each compound was supplemented in the diet at a level of 2 ppm Se for the entire duration of the experiment after MNU dosing.
Se-Allylselenocysteine was the most active and caused a reduction in total
tumor yield by 86%. Se-Methylselenocyteine and
Se-propylselenocysteine were similar but less effective, and both produced a decrease of about 50% in
tumorigenesis. All three compounds were very well absorbed through the gastrointestinal tract. However, more
selenium was excreted in urine after gavaging with
Se-propylselenocysteine or
Se-allylselenocysteine compared with
Se-methylselenocysteine. Analysis of
selenium in the mammary gland and other organs showed that tissue
selenium levels did not appear to be correlated with differences in chemopreventive activity. A
lyase activity capable of catalyzing scission of the Se-alkyl group from the remainder of the
amino acid was demonstrated. This activity was found to be high in liver and kidney, but relatively low in mammary gland and intestine. Minimal variations in
enzyme activity towards each of the substrates were observed. Our results support the concept that Se-alkylselenoamino
acids could be used as precursors for delivering the Se-alkyl moiety and that intrinsic chemical differences in the Se-alkyl substituent of the test compounds are likely to be important determinants of their
biological effects.