Abstract
Modifying effects of taurine, a naturally occurring organosulfur compound, on diethylnitrosamine (DEN) and phenobarbital (PB)‐induced hepatocarcinogenesis were examined in rats. Male F344 rats, 5 weeks old, were divided into 8 groups. Rats of groups 1 through 5 were given i.p. injections of DEN (100 mgAg body weight) once a week for 3 weeks from one week after the start of the experiment. Of them, animals of group 2 received taurine mixed in a basal diet at a concentration of 2000 ppm for the initial 4 weeks, and those of groups 3 and 5 were given the agent starting 4 weeks after the beginning of experiment until the end (24 weeks). Rats in groups 1, 4, 7 and 8 were kept on the basal diet throughout the experiment (24 weeks). Group 6 was given taurine throughout the experiment and group 8 was treated as a vehicle control. Animals of groups 1,2, 3 and 7 received PB in drinking water at a dose of 500 ppm from one week after the end of carcinogen or vehicle treatment. Liver neoplasms were recognized only in DEN‐treated groups. The incidence and average number of liver neoplasms of group 3 were significantly lower than those of group 1. The number of glutathione S‐transferase placenta! form (GST‐P)‐positive foci of group 2 or 3 was significantly smaller than that of group 1 (P < 0.01 or P < 0,005). The average and unit areas of GST‐P‐positive foci in groups 2 and 3 were also significantly smaller than those in group 1 (P< 0.005 and P< 0.0001, P< 0.0001 and P< 0.001, respectively). In this study, the level of ornithine decarboxylase activity in non‐neoplastic liver tissue was reduced by taurine treatment in both the initiation and postinitiation phases. These results suggest that taurine could be a chemopreventive agent for liver neoplasia.
Keywords: Taurine, Chemoprevention, Hepatocarcinogenesis, GST‐P, ODC
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REFERENCES
- 1. ) Wattenberg , L. W. . Guest editorial: Inhibition of chemical carcinogenesis . J. Natl. Cancer Inst. , 48 , 1425 – 1430 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Pilot , H. C. , Barsness , L. and Kitagawa , T.Stages in the process of hepatocarcinogenesis in the rat liver . In “ Carcinogenesis, Vol. 2: Mechanisms of Tumor Promotion and Carcinogenesis ,” ed. , Slaga T. J. , Sivak A. and Boutwell R. K. , pp. 433 – 442 ( 1978. ). Raven Press; , New York . [Google Scholar]
- 3. ) Pitot , H. C. , Barsness , L. , Goldsworthy , T. and Kitagawa , T. . Biochemical characterization of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine . Nature , 271 , 456 – 458 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Wattenberg , L. W. . Chemoprevention of cancer . Cancer Res. , 45 , 1 – 8 ( 1985. ). [PubMed] [Google Scholar]
- 5. ) Graham , S. . Toward a dietary prevention of cancer . Epidemiol. Rev. , 5 , 38 – 50 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Freudenheim , J. L. and Graham , S. . Toward a dietary prevention of cancer . Epidemiol. Rev. , 11 , 229 – 235 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Salt , D. B. and Farber , E. . New principle for the analysis of chemical carcinogenesis . Nature , 263 , 701 – 703 ( 1976. ). [Google Scholar]
- 8. ) Peraino , C. , Staffeldt , E. F. and Ludeman , V. A. . Early appearance of histochemically altered hepatocyte foci and liver tumors in female rat treated with carcinogens one day after birth . Carcinogenesis. , 2 , 463 – 465 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Williams , G. M. . The pathogenesis of rat liver cancer caused by chemical carcinogenesis . Biochim. Biophys. Acta , 605 , 167 – 189 ( 1980. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Kochakian , C. D.Taurine and related sulfur compounds in the reproductive tract of marine animals . In “ Taurine ,” ed. Huxtable R. and Barbeau A. , pp. 375 – 378 ( 1976. ). Raven Press; , New York . [Google Scholar]
- 11. ) Uhe , A. M. , Collier , G. R. and O'dea , K. . A comparison of the effects of beef, chicken and fish protein on satiety and amino acid profiles in lean male subjects . J. Nutr. , 122 , 467 – 472 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Suyama , M. and Yoshizawa , Y. . Free amino acid composition of the skeletal muscle of migratory fish . Bull. Jpn. Soc. Sci. Fish. , 39 , 1339 – 1343 ( 1973. ). [Google Scholar]
- 13. ) Mizushima , S. and Yamori , Y. . Nutritional improvement, cardiovascular diseases and longevity in Japan . Nutr. Health , 8 , 97 – 105 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Yamori , Y. , Nara , Y. , Mizushima , S. , Mano , M. , Sawamura , M. , Kihara , M. and Hiroe , R. . International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group . Nutr. Health , 8 , 77 – 90 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Yamori , Y. , Nara , Y. , Mizushima , S. , Sawamura , M. and Horie , R. . Nutritional factors for stroke and major cardiovascular diseases: international epidemiological comparison of dietary prevention . Health Rep. , 6 , 22 – 27 ( 1994. ). [PubMed] [Google Scholar]
- 16. ) Yamori , Y. , Nara , Y. , Mizushima , S. , Murakami , S. , Ikeda , K. , Sawamura , M. , Nabika , K. and Horie , R. . Gene‐environment interaction in hypertension, stroke and atherosclerosis in experimental models and supportive findings from a world‐wide cross‐sectional epidemiological survey: a WHO‐cardiac study . Clin. Exp. Pharmacol. Physiol. , 20 , 43 – 52 ( 1992. ). [PubMed] [Google Scholar]
- 17. ) Petty , M. A. , Kintz , J. and DiFrancesco , G. F. . The effects of taurine on atherosclerosis development in cholesterolfed rabbits . Eur. J. Pharmacol. , 180 , 119 – 127 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Trachtman , H. , Futterweit , S. and Bienkowski , R. S. . Taurine prevents glucose‐induced lipid peroxidation and increased collagen production in cultured rat mesangial cells . Biochem. Biophys. Res. Commun. , 191 , 759 – 765 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Aruoma , O. I. , Halliwell , B. , Hoey , B. M. and Butler , J. . The antioxidant action of taurine, hypotaurine and their metabolic precursors . Biochem. J. , 256 , 251 – 255 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. ) Talalay , P.The role of enzyme induction against carcinogenesis . In “ Cancer Chemoprevention ,” ed. , Wattenberg L. W. , Lipkin M. , Boone C. W. and Keroff G. J. , pp. 469 – 478 ( 1992. ). CRC Press; , Boca Raton , FL . [Google Scholar]
- 21. ) Reddy , B. S. , Rao , C. V. , Rivenson , A. and Kelloff , G. . Chemoprevention of colon carcinogenesis by organosulfur compounds . Cancer Res. , 53 , 3493 – 3498 ( 1993. ). [PubMed] [Google Scholar]
- 22. ) Wattenberg , L. W.Chemoprevention of cancer by naturally occurring and synthetic compounds . In “ Cancer Chemoprevention ,” ed. , Wattenberg L. W. , Lipkin M. , Boone C. W. and Keroff G. J. , pp. 19 – 39 ( 1992. ). CRC Press; , Boca Raton , FL . [Google Scholar]
- 23. ) Kojima , T. , Tanaka , T. , Kawamori , T. , Hara , A. and Mori , H. . Chemopreventive effects of dietary D, L‐α‐difluoromethylornithine, an ornithine decarboxylase inhibitor, on initiation and postinitiation stages of diethylnitrosamine‐induced rat hepatocarcinogenesis . Cancer Res. , 53 , 3903 – 3907 ( 1993. ). [PubMed] [Google Scholar]
- 24. ) Tanaka , T. , Kojima , T. , Yoshimi , N. and Mori , H. . Chemoprevention of diethylnitrosamine‐induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats . Cancer Res. , 53 , 2775 – 2779 ( 1993. ). [PubMed] [Google Scholar]
- 25. ) Lans , J. I. , Jaszewski , R. , Arlow , F. L. , Tureaud , J. , Luk , G. D. and Majumder , A. P. N. . Supplemental calcium suppresses colonic mucosal ornithine decarboxylase activity in elderly patients with adenomatous polyps . Cancer Res. , 51 , 3416 – 3419 ( 1991. ). [PubMed] [Google Scholar]
- 26. ) Tanaka , T. , Iwata , H. , Niwa , K. , Mori , Y. and Mori , H. . Inhibitory effect of ellagic acid on N‐2‐fluorenylacetamideinduced liver carcinogenesis in male ACI/N rats . Jpn. J. Cancer Res. , 79 , 1297 – 1303 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. ) Tanaka , T. , Mori , Y. , Morishita , Y. , Hara , A. , Ohno , T. , Kojima , T. and Mori , H. . Inhibitory effect of sinigrin and indole‐3‐carbinol on diethylnitrosamine‐induced hepatocarcinogenesis in male ACI/N rats . Carcinogenesis , 11 , 1403 – 1406 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 28. ) Albanes , D. . Total calories, body weight, and tumor incidence in mice . Cancer Res. , 47 , 1987 – 1992 ( 1987. ). [PubMed] [Google Scholar]
- 29. ) Sugie , S. , Tanaka , T. , Mori , H. and Reddy , B. S. . Effect of restricted caloric intake on the development of the azoxymethane‐induced glutathione S‐transferase placental form positive hepatocellular foci in male F344 rats . Cancer Lett. , 68 , 67 – 73 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 30. ) Kitchin , K. T. , Brown , J. L. and Kulkarni , A. P.Ornithine decarboxylase induction and DNA damage as predictive assay for potential carcinogenicity . In “ Chemically Induced Cell Proliferation: Implications for Risk Assessment ,” ed. , Boutwell B. E. , Slaga T. J. , Farland W. and McCIain M. , pp. 137 – 144 ( 1991. ). Wiley‐Liss Inc. , New York . [PubMed] [Google Scholar]
- 31. ) Pegg , A. E. . Recent advances in biochemistry of polyamines in eukaryotes . Biockem. J. , 234 , 249 – 262 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. ) Pegg , A. E. . Polyamine metabolism and its importance in neoplastic growth and as a target for chemotherapy . Cancer Res. , 48 , 759 – 774 ( 1988. ). [PubMed] [Google Scholar]
- 33. ) Liu , P. , Kawada , N. , Mizoguchi , Y. and Morisawa , S. . Arachidonate metabolism in D‐galactosamme or carbon tetrachloride‐induced acute and chronic liver injuries in rats . Gastroenterol. Jpn. , 27 , 624 – 631 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 34. ) Pierson , H. F. , Fisher , J. M. and Rabinovitz , M. . Modulation by taurine of the toxicity of taumustine, a compound with antitumor activity . J. Natl. Cancer Inst. , 75 , 905 – 909 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 35. ) Popp , J. A. and Marsman , D. S.Chemically induced cell proliferation in liver carcinogenesis . In “ Chemically Induced Cell Proliferation: Implications for Risk Assessment ,” ed. , Boutwell B. E. , Slaga T. J. , Farland W. and McClain M. , pp. 389 – 395 ( 1991. ). Wiley‐Liss Inc. , New York . [PubMed] [Google Scholar]
- 36. ) Olson , J. W. and Russell , D. H. . Prolonged induction of hepatic ornithine decarboxylase and its relation to cyclic adenosine 3′:5′‐monophosphate‐dependent protein kinase activation after a single administration of diethylnitrosamine . Cancer Res. , 39 , 3074 – 3079 ( 1979. ). [PubMed] [Google Scholar]
- 37. ) Olson , J. W. and Russell , D. H. . Prolonged ornithine decarboxylase induction in regenerating carcinogentreated liver . Cancer Res. , 40 , 4373 – 4380 ( 1980. ). [PubMed] [Google Scholar]
- 38. ) Pathirana , C. and Grimble , R. F. . Taurine and serine supplementation modulates the metabolic response to tumor necrosis factor α in rats fed a low protein diet . J. Nutr. , 122 , 1369 – 1375 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 39. ) el Tahir , K. E. , Ageel , A. M. and Abu‐Jayyab , A. R. . Effect of taurine on arterial, uterine and cardiac PGI2 and TXA2 synthesis in the rat . Prostaglandins , 33 , 17 – 24 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 40. ) Myers , S. , Bartula , L. and Kalley‐Taylor , B. . The role of prostaglandin I2 and biliary lipids during evolving cholecystitis in the rabbit . Gastroenterology , 104 , 248 – 255 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 41. ) Kimura , H. , Okamoto , K. and Sakai , Y. . Modulatory effects of prostaglandin D2, E2 and F2α on the postsynaptic actions of inhibitory and excitatory amino acids in cerebellar Purkinje cell dendrites in vitro . Brain Res. , 330 , 235 – 244 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 42. ) Kuiper , J. , Casteleyn , E. and Van Berkel , T. J. . Regulation of liver metabolism by intercellular communication . Adv. Enzyme Regul. , 27 , 193 – 208 ( 1988. ). [DOI] [PubMed] [Google Scholar]