Abstract
Naturally occurring and synthetic isothiocyanates are among the most effective chemopreventive agents known. A wide variety of isothiocyanates prevent cancer of various tissues including the rat lung, mammary gland, esophagus, liver, small intestine, colon, and bladder. Mechanistic studies have shown that the chemopreventive activity of isothiocyanates is due to favorable modification of Phase I and Phase II carcinogen metabolism, resulting in increased carcinogen excretion or detoxification and decreased carcinogen DNA interactions. In the majority of studies reported, the isothiocyanate must be present at the time of carcinogen exposure in order to observe inhibition of tumorigenesis. Our studies have focused on the naturally occurring isothiocyanates phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) as inhibitors of lung cancer. The carcinogens employed in these studies have been the major lung carcinogens in tobacco smoke — 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP). Combinations of chemopreventive agents that inhibit tumorigenesis by NNK and BaP in rodents may be effective in addicted smokers. PEITC is an effective inhibitor of lung tumor induction by NNK in F-344 rats and A/J mice. BITC but not PEITC inhibits BaP induced lung tumorigenesis in A/J mice. PEITC is a selective inhibitor of the metabolic activation of NNK in the rodent lung, and studies in smokers who consumed watercress, a source of PEITC, indicate that the metabolic activation of NNK is also inhibited by PEITC in humans. Combinations of chemopreventive agents active against different carcinogens in tobacco smoke may be useful in the chemoprevention of lung cancer.
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References
Sones, K., R. K. Heaney, and G. R. Fenwick, An estimate of the mean daily intake of glucosinolates from cruciferous vegetables in the U. K, J. Sci. Food Agric. 35: 712 (1984).
Chung, F.-L., M. A. Morse, K. L Eklind, and J. Lewis, Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal, Cancer Epidemiol, Biomarkers Prev. 1: 383 (1992).
Sasaki, S., Inhibitory effects by a-naphthylisothiocyanate on liver tumorigenesis in rats treated with 3′-methyl-4-dimethyl-aminoazobenzene, J. Nara Med. Assoc. 14: 101 (1963).
Sidransky, H., N. Ito, and E. Verney, Influence of a-naphthyl-isothiocyanate on liver tumorigenesis in rats ingesting ethionine and N-2-fluorenylacetamide, J. Natl. Cancer Inst. 31: 611 (1966).
Lacassagne, A., L. Hurst, and M. D. Xuong, Inhibition, par deux naphthylisothiocyanates, de l’hepatocancérogenèse produit, chez le rat, par le p-dimethylaminoazobenzene (DAB), C.R. Séances Soc. Biol. Fil. 164: 230(1970).
Ito, N., Y. Hiasa, Y. Konishi, and M. Marugami, The development of carcinoma in liver of rats treated with m-toluylenediamine and the synergistic and antagonistic effects with other chemicals, Cancer Res. 29: 1137 (1969).
Makiura, S., Y. Kamamoto, S. Sugihara, K. Hirao, Y. Hiasa, M. Arai, and N. Ito, Effect of 1-naphthyl isothiocyanate and 3-methylcholanthrene on hepatocarcinogenesis in rats treated with diethylnitrosoamine, Jpn. J. Cancer Res. 64: 101 (1973).
Ito, N., K. Matayoshi, K. Matsumura, A. Denda, T. Kani, M. Arai, and S. Makiura, Effect of various carcinogenic and non-carcinogenic substances on development of bladder tumors in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosoamine, Jpn. J. Cancer Res. 65: 123 (1974).
Wattenberg, L.W., Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds, J. Natl. Cancer Inst. 58: 395 (1977).
Morse, M. A., S. G. Amin, S. S. Hecht, and F.-L. Chung, Effects of aromatic isothiocyanates on tumorigenicity, O 6methylguanine formation, and metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung, Cancer Res. 49: 2894 (1989).
Wattenberg, L. W., Inhibition of carcinogen-induced neoplasia by sodium cyanate, tert-butyl isocyanate, and benzyl isothiocyanate administered subsequent to carcinogen exposure, Cancer Res. 41: 2991 (1981).
Wattenberg, L. W., Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo[a]pyrene on pulmonary and forestomach neoplasia in A/J mice, Carcinogenesis 8: 1971 (1987).
Lin, J.-M., S. Amin, N. Trushin, and S. S. Hecht, Effects of isothiocyanates on tumorigenesis by benzo[a]pyrene in murine tumor models, Cancer Lett. 74: 151 (1993).
Morse, M.A., J.C. Reinhardt, S.G. Amin, S. S. Hecht, G.D. Stoner, and F.-L. Chung, Effect of dietary aromatic isothiocyanates fed subsequent to the administration of 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumorigenicity in mice, Cancer Lett. 49: 225 (1990).
Sugie, S., A. Okumura, T. Tanaka, and H. Mori, Inhibitory effects of benzyl isothiocyanate and benzyl thiocyanate on diethylnitrosamine-induced hepatocarcinogenesis in rats, Jpn. J. Cancer Res. 84: 865 (1993).
Sugie, S., K. Okamoto, A. Okumura, T. Tanaka, and H. Mori, Inhibitory effects of benzyl thiocyanate and benzyl isothiocyanate on methylazoxymethanol acetate-induced intestinal carcinogenesis in rats, Carcinogenesis 15: 1555 (1994).
Morse, M. A., C.-X. Wang, G. D. Stoner, S. Mandal, P.B. Conran, S.G. Amin, S. S. Hecht, and F.-L. Chung, Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in lung of F344 rats by dietary phenethyl isothiocyanate, Cancer Res. 49: 549 (1989).
Morse, M. A., K.I. Eklind, S. G. Amin, S. S. Hecht, and F.-L. Chung, Effects of alkyl chain length on the inhibition of NNKinduced lung neoplasia in A/J mice by arylalkyl isothiocyanates, Carcinogenesis 10: 1757(1989).
Morse, M.A., K.I. Eklind, S. S. Hecht, K.G. Jordan, C.-I. Choi, D. H. Desai, S. G. Amin, and F.-L. Chung, Structureactivity relationships for inhibition of 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone lung tumorigenesis by arylalkyl isothiocyanates in A/J mice, Cancer Res. 51: 1846 (1991).
Morse, M. A., K. E. Eklind, S. G. Amin, and F. L. Chung, Effect of frequency of isothiocyanate administration on inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary ademona formation in A/J mice, Cancer Lett. 62: 77 (1992).
Stoner, G. D., D. Morrissey, Y.-H. Heur, E. Daniel, A. Galati, and S. A. Wagner, Inhibitory effects of phenethyl isothiocyanate on 7V-nitrosobenzylmethylamine carcinogenesis in the rat esophagus, Cancer Res. 51: 2063(1991).
Adam-Rodwell, G., M. A. Morse, and G. D. Stoner, The effects of phenethyl isothiocyanate onbenzo[a]pyrene-induced tumors and DNA adducts in A/J mouse lung, Cancer Lett. 71: 35 (1993).
Jiao, D., K. I. Eklind, C. I. Choi, D. H. Desai, S.G. Amin, and F. L. Chung, Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice, Cancer Res. 54: 4327 (1994).
Zhang, Y, T.W Kensler, C.-G. Cho, G.H. Posner, and P. Talalay, Anticarcinogenic activities of sul-foraphane and structurally related synthetic norbornyl isothiocyanates, Proc. Natl. Acad. Sci. USA 91: 3147(1994).
Hecht, S. S., Chemoprevention by isothiocyanates, J. Cell. Biochem. [Suppl.] 22: 195 (1995).
Yang, C. S., T. J. Smith, and J.-Y Hong, Cytochrome P-450 enzymes as targets for chemoprevention against chemical carcinogenesis and toxicity: opportunities and limitations, Cancer Res. 54: 1982s (1994).
Zhang, Y and P. Talalay, Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms, Cancer Res. 54: 1976s (1994).
Guo, Z., T. J. Smith, E. Wang, K. I. Eklind, F.-L. Chung, and CS. Yang, Structure-activity relationships, of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism and the modulation of xenobiotic-metabolizing enzymes in rats and mice, Carcinogenesis 14: 1167 (1993).
Wingo, P. A., T. Tong, and S. Bolden, Cancer statistics, 1995, CA 45: 8 (1995).
Shopland, D. R., H. J. Eyre, and T. F. Pechachek, Smoking-attributable cancer mortality in 1991: Is lung cancer now the leading cause of death among smokers in the United States?, J. Natl. Cancer Inst. 83: 1142 (1991).
Hecht, S. S., Metabolic activation and detoxification of tobacco-specific nitrosamines-a model for cancer prevention strategies, Drug Metab. Rev. 26: 373 (1994).
Hecht, S. S., S. G. Carmella, P. G. Foiles, and S. E. Murphy, Biomarkers for human uptake and metabolic activation of tobacco-specific nitrosamines, Cancer Res. 54: 1912s (1994).
Doerr-O’Rourke, K., N. Trushin, S. S. Hecht, and G. D. Stoner, Effect of phenethyl isothiocyanate on the metabolism of the tobacco-specific nitrosamine 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone by cultured rat lung tissue, Carcinogenesis 12: 1029 (1991).
Staretz, M. E. and S. S. Hecht, Effects of phenethyl isothiocyanate on the tissue distribution of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone and metabolites in F344 rats, submitted (1995).
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© 1996 Plenum Press, New York
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Hecht, S.S. (1996). Chemoprevention of Lung Cancer by Isothiocyanates. In: Dietary Phytochemicals in Cancer Prevention and Treatment. Advances in Experimental Medicine and Biology, vol 401. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0399-2_1
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DOI: https://doi.org/10.1007/978-1-4613-0399-2_1
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