K. Elbayoumy et al., SYNTHESIS AND EXCRETION PROFILE OF 1,4-[C-14]PHENYLENEBIS(METHYLENE)SELENOCYANATE IN THE RAT, Carcinogenesis (New York. Print), 19(9), 1998, pp. 1603-1607
1,4-Phenylenebis(methylene)selenocyanate (p-XSC) inhibits chemically i
nduced tumors in several laboratory animal models. To understand its m
ode of action, we synthesized p-[C-14]XSC, examined its excretion patt
ern in female CD rats and also the nature of its metabolites. p-[C-14]
XSC was synthesized from alpha,alpha-dibromo-p-[ring-C-14]xylene in 80
% yield, The excretion profile of p-[C-14]XSC (15.8 mg/kg body wt, 200
mu Ci/rat, oral administration, in 1 mi corn oil) in vivo was monitor
ed by measuring radioactivity and selenium content. On the basis of ra
dioactivity, similar to 20% of the dose was excreted in the urine and
68% in the feces over 3 days, The cumulative percentages of the dose e
xcreted over 7 days were 24% in urine and 75% in feces, similar to exc
retion rates of selenium, According to selenium measurement, <1% of th
e dose was detected in exhaled air; radioactivity was not detected, On
ly 15% of the dose was extractable from the feces with EtOAc and was i
dentified as tetraselenocyclophane (TSC), Most of the radioactivity re
mained tightly bound to the feces. Approximately 10% of this bound mat
erial converted to TSC on reduction with NaBH4, Organic soluble metabo
lites in urine did not exceed 2% of the dose; sulfate (9% of urinary m
etabolites) and glucuronic acid (19.5% of urinary metabolites) conjuga
tes were observed but their structural identification is still underwa
y. Co-chromatography with a synthetic standard led to the detection of
terephthalic acid (1,4-benzenedicarboxylic acid) as a minor metabolit
e. The major urinary conjugates contained selenium, Despite the low le
vels of selenium in the exhaled air, the reductive metabolism of p-XSC
to H2Se cannot be ruled out. Identification of TSC in vivo indicates
that a selenol may be a key intermediate responsible for the chemoprev
entive action of p-XSC.