Carcinogenesis, Vol 19, 1603-1607, Copyright © 1998 by Oxford University Press
K El-Bayoumy, P Upadhyaya, OS Sohn, JG Rosa and ES Fiala
1,4-Phenylenebis(methylene)selenocyanate (p-XSC) inhibits chemically
induced tumors in several laboratory animal models. To understand its mode
of action, we synthesized p-[14C]XSC, examined its excretion pattern in
female CD rats and also the nature of its metabolites. p- [14C]XSC was
synthesized from alpha,alpha-dibromo-p-[ring-14C]xylene in 80% yield. The
excretion profile of p-[14C]XSC (15.8 mg/kg body wt, 200 microCi/rat, oral
administration, in 1 ml corn oil) in vivo was monitored by measuring
radioactivity and selenium content. On the basis of radioactivity,
approximately 20% of the dose was excreted in the urine and 68% in the
feces over 3 days. The cumulative percentages of the dose excreted over 7
days were 24% in urine and 75% in feces, similar to excretion rates of
selenium. According to selenium measurement, <1% of the dose was
detected in exhaled air; radioactivity was not detected. Only 15% of the
dose was extractable from the feces with EtOAc and was identified as
tetraselenocyclophane (TSC). Most of the radioactivity remained tightly
bound to the feces. Approximately 10% of this bound material converted to
TSC on reduction with NaBH4. Organic soluble metabolites in urine did not
exceed 2% of the dose; sulfate (9 % of urinary metabolites) and glucuronic
acid (19.5% of urinary metabolites) conjugates were observed but their
structural identification is still underway. Co-chromatography with a
synthetic standard led to the detection of terephthalic acid (1,4-
benzenedicarboxylic acid) as a minor metabolite. The major urinary
conjugates contained selenium. Despite the low levels 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 chemopreventive action of p- XSC.
ARTICLES
Synthesis and excretion profile of 1,4- [14C]phenylenebis(methylene)selenocyanate in the rat
American Health Foundation, Valhalla, NY 10595, USA.
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