Inhibitory effects of isopropyl-2-(1,3-dithietane-2-ylidene)-2- [N-(4-methylthiazol-2-yl)carbamoyl]acetate (YH439) on benzo[a]pyrene-induced skin carcinogenesis and micronucleated reticulocyte formation in mice.
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.
Surh
Y J
YJ
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742, South Korea. surh@plaza.snu.ac.kr
Kim
S G
SG
Liem
A
A
Lee
J W
JW
Miller
J A
JA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D016587:Antimutagenic Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003433:Crosses, Genetic; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D012156:Reticulocytes / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D013844:Thiazoles; C098009:YH 439; D001564:Benzo(a)pyrene