Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1989 Oct;80(10):952–957. doi: 10.1111/j.1349-7006.1989.tb01632.x

Inhibition by Dietary Benzylselenocyanate of Hepatocarcinogenesis Induced by Azoxymethane in Fischer 344 Rats1

Shigeyuki Sugie 1,4, Bandaru S Reddy 2, Karam El‐Bayoumy 3, Takuji Tanaka ✉
PMCID: PMC5917878  PMID: 2515179

Abstract

The effect of dietary benzylselenocyanate (BSC), a novel organoselenium compound and its sulfur analog, benzylthiocyanate (BTC), on hepatocarcinogenesis induced by azoxymethane (AOM) was investigated in male F344 rats. Eighty‐one weanling rats were divided into 3 groups and were raised on a semipurificd diet (control diet). Starting from 5 weeks of age, groups of animals consuming the control diet were fed one of the experimental diets containing 25 ppm BSC or BTC. An additional group was continued on the control diet. At 7 weeks of age, animals were given weekly sc injections of AOM (15 mg/kg body weight once weekly for 2 weeks). One week after the second AOM injection, those groups receiving BSC and BTC diets were transferred to the control diet and continued on this diet until termination of the experiment at 34 weeks after the last AOM injection. For quantitative analysis of enzyme‐altered liver cell foci, glutathione S‐transferase placental form was stained by an immunohistochemical technique. The results indicate that the incidence and the density of the enzyme‐altered foci were significantly lower in AOM‐treated rats fed the diet containing 25 ppm BSC (foci incidence 56%, foci density 2.43/cm2) than in AOM‐treated animals fed the control diet (foci incidence 92%, foci density 4.79/cm2). The incidence of small altered foci was significantly inhibited in rats fed the BTC diet (35%) as compared to those fed the control diet (68%), but the degree of inhibition was more pronounced in animals fed the BSC diet than in those fed the BTC diet.

Keywords: Benzylselenocyanate, Benzylthiocyanate, Chemoprevention, Azoxymethane, Rat hepatocarcinogenesis

Full Text

The Full Text of this article is available as a PDF (387.6 KB).

†

This paper is No. 6 in the series “Selenium in Chemoprevention of Carcinogenesis.”

REFERENCES

  • 1. ) Griffin , A. C.Role of selenium in the chemoprevention of cancer . Adv. Cancer Res. , 29 , 419 – 442 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Fishbein , L.Perspectives in metal carcinogenesis. I. Selenium . Arch. Geschwulstforsch. , 56 , 53 – 78 ( 1986. ). [PubMed] [Google Scholar]
  • 3. ) Ip , C.Selenium and experimental cancer . Ann. Clin. Res. , 18 , 22 – 29 ( 1986. ). [PubMed] [Google Scholar]
  • 4. ) Nelson , A. A , Fitzhugh , O. G. and Calvery , H. O.Liver tumors following cirrhosis caused by selenium . Cancer Res. , 3 , 230 – 236 ( 1943. ). [Google Scholar]
  • 5. ) Schrauzer , G. N. , White , D. A. , McGinness , J. E. , Schneider , C. J. and Bell , L. J.Inhibition of the genesis of spontaneous mammary tumors in C3H mice: effects of selenium and of selenium‐antagonistic elements and their possible role in breast cancer . Bioinorg. Chem. , 6 , 265 – 270 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Schrauzer , G. N. , McGinness , J. E. and Kuehn , K.Effects of temporary selenium supplementation on the genesis of spontaneous mammary tumors in inbred fetal C3H/St mice . Carcinogenesis , 1 , 199 – 201 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Medina , D. and Shepherd , F.Selenium‐mediated inhibition of mouse mammary tumorigenesis . Cancer Lett. , 8 , 241 – 245 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Medina , D. , Lane , H. and Shepherd , F.Effects of selenium on mouse mammary tumorigenesis and glutathione peroxidase activity . Anticancer Res. , 1 , 377 – 382 ( 1981. ). [PubMed] [Google Scholar]
  • 9. ) Clayton , C. C. and Baumann , C. A.Diet and azo dye tumors: effect of diet during a period when the dye is not fed . Cancer Res. , 9 , 575 – 582 ( 1949. ). [PubMed] [Google Scholar]
  • 10. ) Harr , J. R. , Exon , J. H. , Whanger , P. D. and Weswig , P. H.Effect of dietary selenium on N‐2‐fluorenylacetamide (FAA)‐induced cancer in vitamin E supplemented, selenium‐depleted rats . din. ToxicoL , 5 , 187 – 194 ( 1972. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Griffin , A. C. and Jacob , M. M.Effect of selenium on azo‐dye hepatocarcinogenesis . Cancer Lett. , 3 , 177 – 181 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Grant , K. E. , Conner , M. W. and Newberne , P. M.Effects of dietary sodium selenite upon lesions induced by repeated small doses of aflatoxin B1 . ToxicoL Appl. Pharmacol , 41 , 166 ( 1977. ). [Google Scholar]
  • 13. ) Marshall , M. V. , Jacobs , M. M. and Griffin , A. C.Selenium effects on the carcinogenicity and metabolism of 2‐acetylaminofluorene . Proc. Am. Assoc. Cancer Res. , 9 , 75 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Balansky , R. M. and Hadsiolov , D. H.Inhibition of hepatocarcinogenic action of diethylnitrosamine in rats by sodium selenite . C.R. Acad. Bulg. Sci. , 32 , 697 – 698 ( 1979. ). [Google Scholar]
  • 15. ) Thompson , H. J. and Becci , P. J.Selenium inhibition of N‐methyl‐N‐nitrosourea‐induced mammary carcinogenesis in the rat . J. Natl. Cancer Inst. , 65 , 1299 – 1301 ( 1980. ). [PubMed] [Google Scholar]
  • 16. ) Ip , C. and Sinha , D. K.Enhancement of mammary tumorigenesis by dietary selenium deficiency in rats with a high polyunsaturated fat intake . Cancer Res. , 41 , 31 – 34 ( 1980. ). [PubMed] [Google Scholar]
  • 17. ) Ip , C.Factors influencing the anticarcinogenic efficacy of selenium in dimethylbenz[a] anthracene‐induced mammary tumorigenesis in rats . Cancer Res. , 41 , 2683 – 2686 ( 1981. ). [PubMed] [Google Scholar]
  • 18. ) Nigro , N. D. , Bull , A. W. , Wilson , P. J. , Suollier , B. K. and Alousi , M. A.Combined inhibitors of carcinogenesis: effect on azoxymethane‐induced intestinal cancer in rats . J. Natl. Cancer Inst. , 69 , 103 – 107 ( 1982. ). [PubMed] [Google Scholar]
  • 19. ) Balansky , R. M. , Blagoeva , P. M. and Mirtcheva , Z.The influence of selenium and caffeine on chemical carcinogenesis in rats, mutagenesis in bacteria, and unschedule DNA synthesis in human lymphocytes . Biol. Trace. Elem. Res. , 5 , 331 – 343 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Reddy , B. S. , Tanaka , T. and El‐Bayoumy , K.Inhibition effect of dietary p‐methoxybenzenselenol on the initiation stage of azoxymethane‐induced colon and kidney carcinogenesis in female F344 rats. J . Natl. Cancer Inst. , 74 , 1325 – 1328 ( 1985. ). [PubMed] [Google Scholar]
  • 21. ) Tanaka , T. , Reddy , B. S. and El‐Bayoumy , K.Inhibition of dietary organoselenium, p‐methoxybenzeneselenol, of hepatocarcinogenesis induced by azoxymethane in rats . Jpn. J. Cancer Res. , 76 , 462 – 467 ( 1985. ). [PubMed] [Google Scholar]
  • 22. ) Buell , D. N.Potential hazards of selenium as a chemopreventive agent . Semin. Oncol. , 10 , 311 – 321 ( 1983. ). [PubMed] [Google Scholar]
  • 23. ) Thompson , H. J. , Meeker , L. D. and Kokoska , S.Effect of an inorganic and organic form of dietary selenium on the promotional stage of mammary carcinogenesis in the rat . Cancer Res. , 44 , 2803 – 2806 ( 1984. ). [PubMed] [Google Scholar]
  • 24. ) El‐Bayoumy , K.Effects of organoselenium compounds on induction of mouse forestomach tumors by benzo[a]‐pyrene . Cancer Res. , 45 , 3631 – 3635 ( 1985. ). [PubMed] [Google Scholar]
  • 25. ) Reddy , B. S. , Sugie , S. , Maruyama , H. , El‐Bayoumy , K. and Marra , P.Chemoprevention of colon carcinogenesis by dietary organoselenium, benzylselenocyanate, in F344 rats . Cancer Res. , 47 , 5901 – 5904 ( 1987. ). [PubMed] [Google Scholar]
  • 26. ) American Institute of Nutrition. Second report of the Ad Hoc Committee on Standards for Nutritional Studies . J. Nutr. , 110 , 1726 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Reddy , B. S. and Maeura , Y.Tumor promotion by dietary fat in azoxymethane‐induced colon carcinogenesis in female F344 rats: influence of amount and source of dietary fat . J. Natl. Cancer Inst. , 72 , 745 – 750 ( 1980. ). [PubMed] [Google Scholar]
  • 28. ) Williams , G. M.The pathogenesis of rat liver cancer caused by chemical carcinogenesis . Biochim. Biophys. Ada , 605 , 167 – 189 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Moore , M. A. , Nakagawa , K. , Satoh , K. , Ishikawa , K. and Sato , K.Single GST‐P positive liver cells—putative initiated hepatocytes . Carcinogenesis , 8 , 483 – 486 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) Medina , D.Mechanisms of selenium inhibition of tumorigenesis . J. Am. Coll. ToxicoL , 5 , 21 – 26 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Marshall , M. V. , Arnott , M. S. , Jacob , M. M. and Griffin , A. C.Selenium effects on the carcinogenicity and metabolism of 2‐acetylaminofluorene . Cancer Lett. , 7 , 331 – 338 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Fiala , E. S.Investigations into the metabolism and mode of action of the colon carcinogens, 1,2‐dimethylhydrazine and azoxymethane . Cancer , 40 , 2436 – 2445 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 33. ) Fiala , E. S. , Caswell , N. , Sohn , O. S. , Felder , M. R. , McCoy , G. D. and Weisburger , J. H.Non‐alcohol dehydrogenase‐mediated metabolism of methylazoxy‐methanol in the deer mouse , Peromyscus maniculatus, Cancer Res. , 44 , 2885 – 2891 ( 1984. ). [PubMed] [Google Scholar]
  • 34. ) Fiala , E. S. and Stathopoulos , C.Metabolism of methylazoxymethanol acetate in the F344 rat strain‐2 guinea pig and its inhibition by pyrazole and disulfiram . J. Cancer Res. Clin. Oncol. , 108 , 129 – 134 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 35. ) Oravec , C. T. , Jones , C. A. and Huberman , E.Activation of the colon carcinogens 1,2‐dimethylhydrazine in the rat colon cell‐mediated mutagenesis assay . Cancer Res. , 46 , 5068 – 5071 ( 1986. ). [PubMed] [Google Scholar]

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

RESOURCES