Polycyclic aromatic hydrocarbons (PAH) are an important group of carcinogens that are likely to be involved as one of the causes of lung cancer in smokers and occupationally exposed individuals. Previous studies have shown that benzyl isothiocyanate (BITC), administered by gavage, is a good inhibitor of lung tumorigenesis in A/J mice induced by benzo[a]pyrene (BaP), a typical PAH carcinogen. In this study, we evaluated the effects of BITC on lung tumor induction in A/J mice by two other carcinogenic PAH in cigarette smoke - 5-methylchrysene (5-MeC) and dibenz[a,h]anthracene (DBahA). We also compared the effects of BITC with two other well known chemopreventive agents - butylated hydroxyanisole (BHA) and sulforaphane. In experiment 1, groups of A/J mice were treated by gavage once weekly for 8 weeks with BaP (3μmol) or 5-MeC (2μmol) or DBahA (1μmol) in 0.1ml cottonseed oil. Fifteen minutes before each treatment, the mice were gavaged with 0.1ml cottonseed oil or 0.1ml cottonseed oil containing 13.4μmol or 6.7μmol of BITC. The experiment was terminated 19 weeks after the final carcinogen treatment. BITC significantly reduced lung tumor multiplicity in all PAH-treated groups by 63.5-90.6%. In experiment 2, groups of A/J mice were treated with BaP or BITC and BaP as in experiment 1, or with BHA or sulforaphane at doses equimolar to those of BITC. BITC was significantly more effective as an inhibitor of lung tumor induction than either BHA or sulforaphane. These results firmly establish gavaged BITC as a strong inhibitor of lung tumorigenesis induced in A/J mice by PAH, and support its further development for chemoprevention of smoking-induced lung cancer.
Bibliographical noteFunding Information:
This study was supported by grant CA-46535 from the National Cancer Institute. Stephen S. Hecht is an American Cancer Society Research Professor, supported by ACS grant RP-00-138. We thank Robin Bliss, University of Minnesota Cancer Center Biostatistics core facility, for statistical analyses. The Cancer Center is supported in part by Cancer Center Support Grant CA-77598.
- A/J mouse lung tumors
- Benzyl isothiocyanate
- Butylated hydroxyanisole
- Polycyclic aromatic hydrocarbons