Chemoprevention of vinyl carbamate-induced lung tumors in strain A mice.
The ability of potential chemopreventive agents to prevent vinyl carbamate-induced lung tumors was determined in 2 different experiments. Female strain A mice administered intraperitoneally either a single injection of 60 mg/kg vinyl carbamate that induced 24.0 +/- 1.72 tumors/mouse at 24 weeks or 2 injections of 16 mg/kg vinyl carbamate each (32 mg/kg total dose) that induced 43.2 +/- 3.2 tumors/mouse at 20 weeks. Lung carcinomas were found as early as 16 weeks. Dexamethasone and piroxicam provided in the diet were found to significantly inhibit lung tumors induced by 60 mg/kg vinyl carbamate at 24 weeks whereas myo-inositol also provided in the diet, did not significantly inhibit tumor formation. In animals given 6 16-mg/kg doses of vinyl carbamate, tumor multiplicity was reduced roughly 25% by alpha-difluoromethylornithine and green tea and reduced 50% by dexamethasone and piroxicam. Combinations of these agents were also tested using a total dose of 32 mg/kg of vinyl carbamate. Although alpha-difluoromethylornithine and green tea did not result in a significant inhibition of lung tumor formation if used alone, the combination of alpha-difluoromethylornithine and green tea resulted in a significant reduction of tumor multiplicity. The combinations of alpha-difluoromethylornithine or green tea with either dexamethasone or piroxicam or the combination of dexamethasone and piroxicam did not decrease tumor multiplicity greater than achieved by dexamethasone and piroxicam alone. In summary, selected chemopreventive agents previously shown to inhibit lung tumors by other chemical carcinogens also inhibited vinyl carbamate-induced lung tumors.
Gunning
W T
WT
Department of Pathology, Block Health Science Building, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614-5806, USA. wgunning@mco.edu
Kramer
P M
PM
Lubet
R A
RA
Steele
V E
VE
Pereira
M A
MA
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D018890:Chemoprevention; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000627:therapeutic use; D005260:Female; D007294:Inositol / Q000008:administration & dosage / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D008517:Phytotherapy; D010894:Piroxicam / Q000008:administration & dosage / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000648:ultrastructure; D013662:Tea / Q000627:therapeutic use; D014520:Urethane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D011663:Pulmonary Surfactants; D013662:Tea; D010894:Piroxicam; D014520:Urethane; D007294:Inositol; D003907:Dexamethasone; C017963:vinyl carbamate; D000518:Eflornithine