Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds.
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.
Sumiyoshi
H
H
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Wargovich
M J
MJ
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*
D000970:Antineoplastic Agents; D002273:Carcinogens; D004127:Dimethylhydrazines; D004220:Disulfides; D013440:Sulfides; C065299:S-allylcysteine; D019813:1,2-Dimethylhydrazine; D003545:Cysteine