Chemoprevention by lipoxygenase and leukotriene pathway inhibitors of vinyl carbamate-induced lung tumors in mice.
5-Leukotriene pathway inhibitors, Accolate, MK-886, and Zileuton, were evaluated as chemopreventive agents in female strain A mice. The mice were administered by injection vinyl carbamate (2 x 16 mg/kg) to induce lung tumors. Two weeks later, they received in their diet Accolate (270 and 540 mg/kg), MK-886 (30 mg/kg), Zileuton (600 and 1200 mg/kg), or combinations containing the lower concentration of two agents. Thirteen weeks later, Accolate, Zileuton (only the high concentration), and combinations of Zileuton with either Accolate or MK-886 reduced lung tumor multiplicity. At week 43, MK-886, Accolate, and Zileuton reduced lung tumor multiplicity by 37.8, 29.5, and 28.1%, respectively. They also decreased the size of the tumors and the yield of carcinomas. These results demonstrate that leukotriene inhibitors prevent lung tumors and slow the growth and progression of adenomas to carcinoma; leukotriene inhibitors warrant further consideration for potential use in humans.
Gunning
William T
WT
Department of Pathology, Medical College of Ohio, Toledo, Ohio 43614, USA. wgunning@mco.edu
Kramer
Paula M
PM
Steele
Vernon E
VE
Pereira
Michael A
MA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology; D014520:Urethane / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D002722:Chlorobenzenes
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D006918:Hydroxyurea; D007211:Indoles; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D014520:Urethane; C060893:MK-886; D002722:Chlorobenzenes; C017963:vinyl carbamate; C063449:zileuton; C062735:zafirlukast