Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Aug;84(8):865–870. doi: 10.1111/j.1349-7006.1993.tb02059.x

Inhibitory Effects of Benzyl Isothiocyanate and Benzyl Thiocyanate on Diethylnitrosamine‐induced Hepatocarcinogenesis in Rats

Shigeyuki Sugie 1,✉, Ataru Okumura 1, Takuji Tanaka 1, Hideki Mori 1
PMCID: PMC5919262  PMID: 8104919

Abstract

The effects of two aromatic thiocyanates, benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC), on diethylnitrosamine (DEN)‐induced hepatocarcinogenesis were examined in rats. A total of 108 male ACI/N rats, 5 weeks old, were divided into 6 groups (18 rats in each). Group 1 was given a single i.p, injection of DEN (200 mg/kg body weight) one week after the start of the experiment and then kept on the basal diet until the end of the experiment (1 year). Groups 2 and 3 were treated with DEN and received dietary BITC (100 ppm) or BTC (100 ppm), respectively, throughout the experimental duration. Groups 4 and 5 were not given the carcinogen and were fed the diet containing BITC or BTC, respectively. Group 6 was kept on the basal diet alone and served as a control. Liver neoplasms were seen in Groups 1, 2 and 3. Incidence and average number of liver neoplasms in Group 2 were significantly smaller than in Group 1 (P<0.0005 and P<0.001, respectively). The incidence of liver neoplasms in Group 3 was slightly lower than in Group 1, although the difference was not statistically significant. The numbers of glutathione S‐transferase placental form (GST‐P)‐positive foci in Group 2 and γ‐glutarnyltranspepridase (GGT)‐positive foci in Groups 2 and 3 were significantly smaller than those in Group 1 (P<0.001). The average and unit areas of GST‐P‐ or GGT‐positive foci in Group 2 or 3 were also significantly smaller than those in Group 1 (P<0.05). These results suggest that BITC and BTC are chemopreventive agents for DEN‐induced liver tumorigenesis.

Keywords: Benzyl isothiocyanate, Benzyl thiocyanate, Chemoprevention, Hepatocarcinogenesis

Full Text

The Full Text of this article is available as a PDF (344.0 KB).

References

  • 1.Wattenberg , L. W.Guest Editiorial: Inhibition of chemical carcinogenesis . J. Natl. Cancer Inst. , 60 , 1425 – 1430 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 2.Wattenberg , L. W.Chemoprevention of cancer . Cancer Res. , 45 , 1 – 8 ( 1985. ). [PubMed] [Google Scholar]
  • 3.Graham , S.Toward a dietary prevention of cancer . Epidemiol. Rev. , 5 , 38 – 50 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 4.Freudenheim , J. L. and Graham , S.Toward a dietary prevention of cancer . Epidemiol. Rev. , 11 , 229 – 235 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 5.Tanaka , T. , Nishikawa , A. , Shima , H. , Sugie , S. , Shinoda , T. , Yoshimi , N. , Iwata , H. and Mori , H.Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E‐5166), or coffee on hepatocarcinogenesis in rats and hamsters . In “ Antimutagenesis and Anticarcinogenests Mechanisms II ,” ed. Kuroda Y. , Shankel D. M. and Waters M. D. , pp. 429 – 440 ( 1990. ). Plenum Press; , New York. [DOI] [PubMed] [Google Scholar]
  • 6.Fenwick , G. R. , Heaney , R. K. and Mullin , W. J.Glucosinolates and their breakdown products in food and food plants . CRC Crit. Rev. Food Sci. Nutr. , 18 , 123 – 201 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 7.Wattenberg , L. W.Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds . J. Natl. Cancer Inst. , 58 , 395 – 398 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 8.Wattenberg , L. W.Inhibition of carcinogen‐induced neoplasia by sodium cyanate, ferf‐butyl isocyanate, and benzyl isothiocyanate administered subsequent to carcinogen exposure . Cancer Res. , 41 , 2991 – 2994 ( 1981. ). [PubMed] [Google Scholar]
  • 9.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 – 1973 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 10.Sugie , S. , Reddy , B. S. , El‐Bayoumy , K. and Tanaka , T.Inhibition by dietary benzylselenocyanate of hepatocarcinogenesis induced azoxymethane in Fischer 344 rats . Jpn. J. Cancer Res. , 80 , 952 – 957 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Sugie , S. , Yoshimi , N. , Okumura , A. , Tanaka , T. and Mori , H.Modifying effects of benzyl isothiocyanate and benzyl thiocyanate on DNA synthesis in primary culture of rat hepatocytes . Carcinogenesis , 14 , 281 – 283 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 12.Ruttenberg , A. M. , Kim , H. , Fischbeim , J. W. , Hanbers , J. S. , Wasserkrug , H. L. and Seligman , A. M.Histochemical and ultrastructural administration of γ‐glutamyItranspeptidase activity . J, Histochem. Cytochem. , 17 , 517 – 526 ( 1969. ). [DOI] [PubMed] [Google Scholar]
  • 13.Williams , G. M.The pathogenesis of rat liver cancer caused by chemical carcinogenesis . Biochim. Biophys. Acta , 605 , 167 – 189 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 14.Dragan , Y. P. and Pitot , H. C.The role of the stages of initiation and promotion in phenotypic diversity during hepatocarcinogenesis in the rat . Carcinogenesis , 13 , 739 – 750 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 15.Albanes , D.Total calories, body weight, and tumor incidence in mice . Cancer Res. , 47 , 1987 – 1992 ( 1987. ). [PubMed] [Google Scholar]
  • 16.Glauert , H. P. and Pitot , H. C.Influence of dietary fat on the promotion of diethylnitrosamine‐induced hepatocarcinogenesis in female rats . Proc. Soc. Exp. Biol. Med. , 181 , 498 – 506 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 17.Ito , N. , Fukushima , S. and Tsuda , H.Carcinogenicity and modification of the carcinogenic response by BHA, BHT, and other antioxidants . CRC Crit. Rev. Toxicol. , 15 , 109 – 150 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 18.Ito , N. and Hirose , M.Antioxidants — carcinogenic and chemopreventive properties . Adv. Cancer Res. , 53 , 247 – 302 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 19.Thamavit , W. , Tatematsu , M. , Ogiso , T. , Mera , Y. , Tsuda , H. and Ito , N.Dose‐dependent effects of butylated hydroxyanisole, butylated hydroxytoluene and ethoxyquin in induction of foci of rat liver cells containing the placental form of glutathione S‐transferase . Cancer Lett. , 27 , 295 – 303 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 20.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]
  • 21.Morse , M. A. , Wang , C‐X. , Stoner , G. D. , Swapna , M. , Conran , P. B. , Amin , S. G. , Hecht , S. S. and Chung , F‐L.Inhibition of 4‐(methylnitrosamino)‐l‐(3‐pyridyl)‐l‐butanone‐induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate . Cancer Res. , 49 , 549 – 553 ( 1989. ). [PubMed] [Google Scholar]
  • 22.Chung , F‐L. , Wang , M. and Hecht , S. S.Effect of dietary indoles and isothiocyanates on N‐nitrosodimethylamine and 4‐(methylnitrosamine)‐l‐(3‐pyridyl)‐l‐butanone α‐hydroxylation and DNA methyiation in rat liver . Carcinogenesis , 6 , 539 – 543 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 23.Morse , M. A. , Wang , C‐X. , Amin S. G. , Hecht S. S. and Chung , F‐L.Effects of dietary sinigrin or indole‐3‐carbinol on O6‐methylguanine‐DNA‐transmethylase activity and 4‐(methylnitrosamino)‐l‐(3‐pyridyl)‐l‐butanoneinduced DNA methylation and tumorigenicity in F344 rats . Carcinogenesis , 9 , 1891 – 1895 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 24.Sparnins , V. L. , Venegas , P. L. and Wattenberg , L. W.Glutathione S‐transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents . J. Natl. Cancer Inst. , 68 , 493 – 496 ( 1982. ). [PubMed] [Google Scholar]
  • 25.Bradfield , C. A. and Bjeldanes , L. F.Effect of dietary indole‐carbinol on intestinal and hepatic monooxygenase, glutathione S‐transferase and epoxide hydrolase activities in the rat . Food Chem. Toxicol. , 22 , 977 – 982 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 26.McDanell , R. , McLean , A. E. M. , Hanley , A. B. , Heaney , R. K. and Fenwick , G. R.Chemical and biological properties of indole glucosinolates (glucobrassicins): a review . Food Chem. Toxicol. , 26 , 59 – 70 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 27.Chung , F‐L. , Juchaz , A. , Vitarius , J. and Hecht , S. S.Effects of dietary compounds on α‐hydroxylation of N‐nitrosopyrrolidine and Napos;‐nitrosonornicotine in rat target tissues . Cancer Res. , 44 , 2924 – 2928 ( 1984. ). [PubMed] [Google Scholar]
  • 28.Hunter , A. L. and Neal , R. A.Inhibition of hepatic mixed‐function oxidase activity in vitro by various thionosulfur containing compounds . Biochem. Pharmacol. , 24 , 2199 – 2205 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 29.Fiala , E. S. , Joseph , C. , Sohn , O‐S. , El‐Bayoumy , K. and Reddy , B. S.Machanism of benzylselenocyanate inhibition of azoxymethane‐induced colon carcinogenesis in F344 rats . Cancer Res. , 51 , 2826 – 2830 ( 1991. ). [PubMed] [Google Scholar]
  • 30.Nayini , J. R. , Sugie , S. , El‐Bayoumy , K. , Rao , C. V. , Rigotty , J. , Sohn , O‐S. and Reddy , B. S.Effect of dietary benzylselenocyanate on azoxymethane induced colon carcinogenesis in male F344 rats . Nutr. Cancer , 15 , 129 – 139 ( 1991. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES