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Prevention of mouse lung tumors by targretin
Author(s) -
Pereira Michael A.,
Kramer Paula M.,
Nines Ronald,
Liu Yue,
Alyaqoub Fadel S.,
Gunning William T.,
Steele Ver E.,
Lubet Ronald A.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21618
Subject(s) - carbamate , carcinogen , medicine , lung , lung cancer , ratón , pharmacology , chemistry , biochemistry
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. © 2005 Wiley‐Liss, Inc.