title: Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds.
abstract: Organosulfur compounds (OSCs) present in garlic and onion oil have been shown to inhibit chemical carcinogenesis. In this study, we compared the chemopreventive efficacy of five lipid- and four water-soluble OSCs using the murine nuclear aberration assay. Administration of diallyl sulfide and S-allyl cysteine p.o. at a dose of 200 mg/kg 3 h prior to i.p. 1,2-dimethylhydrazine (DMH) injection (20 mg/kg) significantly inhibited colonic nuclear damage in female C57Bl/6J mice by 47% and 36%, respectively. The inhibitory effect of S-allyl cysteine was found to be dose dependent. The other OSCs did not affect the level of DMH-induced nuclear toxicity. Furthermore, the incidence and frequency of colonic tumors induced by DMH (20 mg/kg, 10 weekly i.p. injections) in female CF-1 mice were significantly inhibited by S-allyl cysteine pretreatment, given 3 h prior to each carcinogen injection. These data indicate that the allyl group coupled to a single sulfur atom might play an important structural role in inhibition of DMH-induced colonic nuclear toxicity and carcinogenesis. OSCs containing allyl groups stimulated glutathione S-transferase activity in both the liver and colon. However, their saturated analogues stimulated little or no hepatic and colonic glutathione S-transferase activity. Induction of hepatic and colonic glutathione S-transferase might assist in detoxification of carcinogens and could be necessary for some aspects of chemoprevention.
authors.affiliation: Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: H
authors.initials: H
authors.lastname: Sumiyoshi
authors.forename: M J
authors.initials: MJ
authors.lastname: Wargovich
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D000970:Antineoplastic Agents; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D003545:Cysteine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004127:Dimethylhydrazines; D004220:Disulfides / Q000627:therapeutic use*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D004127:Dimethylhydrazines; D004220:Disulfides; D013440:Sulfides; C065299:S-allylcysteine; D019813:1,2-Dimethylhydrazine; D003545:Cysteine