Recently, a great deal of attention has been devoted to organosulfur compounds with potential
cancer chemopreventive properties. Many
sulfur-containing substances present in Brassica plants have been reported to possess striking anticarcinogenic and antimutagenic activities. Besides naturally occurring organosulfur compounds, certain synthetic
sulfur-containing
pharmaceuticals, such as
oltipraz and
sulindac, are known to exert substantial chemopreventive or chemoprotective effects. Isopropyl-2-(1, 3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2-yl)carbamoyl ]
acetate (
YH439) was initially developed for its possible use as a hepatoprotectant. The compound has been found to up-regulate the expression of
cytochrome P-450 IA1 [I.J. Lee, K.S. Jeong, B.J. Roberts, A.T. Kallarakal, P. Fernandez-Salguero, F.J. Gonzalez, B.J. Song, Transcriptional induction of the
cytochrome P-450 1A1 gene by a thiazolium compound
YH439, Mol. Pharmacol. 49 (1996) 980-988.] which plays a pivotal role in metabolism of the majority of polycyclic aromatic
carcinogens and
mutagens, such as
benzo[a]pyrene (B[a]P). In the present study, we found that
oral administration of
YH439 to CD-1 mice significantly suppressed B[a]P-initiated skin
tumorigenesis. B[a]P-induced formation of micronuclei in mouse peripheral reticulocytes was also attenuated by
YH439 pretreatment. Likewise,
diallyl sulfide, a major volatile
thioether present in garlic, also protected against B[a]P-induced skin
tumorigenesis and micronucleated reticulocyte formation in mice.