Prevention of mouse lung tumors by targretin.
Targretin has indicated chemotherapeutic activity against nonsmall-cell lung cancer and chemoprevention in rat mammary gland. Therefore, targretin was evaluated for the prevention of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) and vinyl carbamate-induced lung tumors in female strain A mice. Three experiments were performed: (i) a dose-response study with vinyl carbamate-induced tumors; (ii) a limited treatment study also with vinyl carbamate and (iii) prevention of NNK-induced tumors. In the dose-response study, 0, 10, 30, 100 and 300 mg/kg targretin were administered after vinyl carbamate. Dose levels of 30 mg/kg and greater significantly decreased tumor multiplicity by >19%. However, the efficacy of 30 and 300 mg/kg was not significantly different demonstrating a shallow dose-response relationship. In the limited treatment study, 200 mg/kg targretin was administered to the mice from 4-13, 4-19, 4-25 and 23-25 weeks after vinyl carbamate. Administering targretin from weeks 4-19 and 4-25 decreased the multiplicity of tumors from 35.3 +/- 1.43 to 29.1 +/- 1.51 and 25.0 +/- 0.93, respectively, and along with administering it from weeks 23-25 decreased tumor size. In the third study, when targretin (100 and 300 mg/kg) was administered for 3 weeks after NNK followed by a 20 weeks holding period, tumor multiplicity was reduced from 10.6 +/- 1.13 to 6.38 +/- 0.75 and 4.60 +/- 0.70, respectively. Hence, targretin demonstrated both preventive and therapeutic activity with respect to mouse lung tumors supporting its further development as a preventive and therapeutic agent for lung cancer.
Pereira
Michael A
MA
Division of Hematology and Oncology, Ohio State University, College of Medicine, Columbus, OH 43210, USA. Pereira-1@medctr.osu.edu
Kramer
Paula M
PM
Nines
Ronald
R
Liu
Yue
Y
Alyaqoub
Fadel S
FS
Gunning
William T
WT
Steele
Vernon E
VE
Lubet
Ronald A
RA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000077610:Bexarotene; D018890:Chemoprevention; D004305:Dose-Response Relationship, Drug; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control*; D051379:Mice; D009374:Neoplasms, Experimental / Q000517:prevention & control; D009602:Nitrosamines / Q000008:administration & dosage; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014520:Urethane / Q000008:administration & dosage / Q000031:analogs & derivatives
D016588:Anticarcinogenic Agents; D009602:Nitrosamines; D013764:Tetrahydronaphthalenes; D014520:Urethane; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C017963:vinyl carbamate; D000077610:Bexarotene