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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1998 Nov;89(11):1113–1117. doi: 10.1111/j.1349-7006.1998.tb00505.x

Modulation of Dihydroxy‐di‐n‐propylnitrosamine‐induced Liver Lesion Development in Opisthorchis‐infected Syrian Hamsters by Praziquantel Treatment in Association with Butylated Hydroxyanisole or Dehydroepiandrosterone Administration

Malcolm A Moore 1,✉, Witaya Thamavit 2, Danai Tiwawech 3, Nobuyuki Ito 4, Hiroyuki Tsuda 1
PMCID: PMC5921716  PMID: 9914779

Abstract

The effects of praziquantel coupled with dehydroepiandrosterone (DHEA) or butylated hydroxyanisole (BHA) administration 16 weeks subsequent to dihydroxy‐di‐n‐propylnitrosamine (DHPN) treatment and infection with Opisthorchis viverrini (OV) on lesion development in the liver of Syrian hamsters were investigated. Animals were given 80 OV metacercariae and then two i.p. injections of DHPN (500 mg/kg body weight) 4 and 5 weeks thereafter. At week 16, groups received praziquantel (250 mg/kg, i.g.) and were placed on normal diet or diet supplemented with BHA (1%) or DHEA (0.6%) until they were killed at week 24. Histopathological assessment revealed that, whereas antihelminthic treatment alone resulted in a clear reduction in hepatocellular lesion development, effects on cholangiocellular lesions were equivocal. BHA and DHEA, in contrast, were both associated with a significant reduction in frequency of cholangiofibrosis and cholangiocellular carcinoma. The former chemical, however, increased the numbers of liver nodules while the hormone brought about a decrease as well as a shift in the phenotype of the lesions. The results thus indicate that although cholangiocellular lesion development may, unlike generation of hepatocellular nodules, be to a certain extent independent of the continued presence of parasite, it can be influenced by exogenous treatments.

Keywords: Opisthorchis viverrini, Liver cancer, Prevention, Butylated hydroxyanisole, Dehydroepiandrosterone

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REFERENCES

  • 1. ) Hou , P. C.The relationship between primary liver cancer and infestation with Clonorchis sinensis . J. Pathol. Bact. , 72 , 239 – 246 ( 1956. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Kim , Y , II , Yang , D. H. and Chang , K. R.Clonorchis sinensis infestation and cholangiocarcinoma of the liver in Korea: epidemiological and pathological reappraisal of 495 consecutive primary carcinomas of the liver in Seoul and Pusan areas . Seoul J. Med. , 15 , 247 – 253 ( 1974. ). [Google Scholar]
  • 3. ) Kurathong , S. , Lerdvirasirikul , P. , Wougpaitoon , V. , Pramoolsinsap , C. , Kanjanapitak , A. , Varawithaya , W. , Phupradit , P. , Bunyaratvej , S. , Upatham , S. and Brockelman , W. Y.Opisthorchis viverrini infection and cholangiocarcinoma: a prospective, case‐control study . Gastroenterology , 89 , 151 – 156 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Harinasuta , C. and Harinasuta , T.Opisthorchis viverrini: life cycle, intermediate hosts, transmission to man and geographical distribution in Thailand . Arzneim-Forsch/Drug Res. , 34 , 1164 – 1167 ( 1984. ). [PubMed] [Google Scholar]
  • 5. ) Migasena , P. and Changbumrung , S.The role of nitrosamines in the causation of primary carcinoma . J. Med. Assoc. Thailand , 57 , 175 – 178 ( 1974. ). [PubMed] [Google Scholar]
  • 6. ) Shank , R. C. , Gordon , J. E. , Wogan , G. N. , Nondasuta , A. and Subhmani , B.Dietary aflatoxins and human liver cancer. III. Field survey of rural Thai families for ingested aflatoxins . Food Cosmet. Toxicol. , 10 , 71 – 76 ( 1972. ). [Google Scholar]
  • 7. ) Migasena , P. , Reaunsuwan , W. and Changbumrung , S.Nitrates and nitrites in local Thai preserved protein foods . J. Med. Assoc. Thailand , 63 , 500 – 505 ( 1980. ). [PubMed] [Google Scholar]
  • 8. ) Bhamarapravati , N. , Thamavit , W. and Vajrasthira , S.Liver changes in hamsters infected with a liver fluke of man, Opisthorchis viverrini . Am. J. Trop. Med. Hyg. , 27 , 787 – 794 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Evans , H. , Bourgeois , C. H. , Comer , D. S. and Keshamras , N.Biliary tract changes in opisthorchiasis . Am. J. Trop. Med. Hyg. , 20 , 667 – 671 ( 1971. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Thamavit , W. , Bhamarapravati , N. , Sahaphong , S. , Vajrasthira , S. and Angsubhakorn , S.Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini‐infected Syrian golden hamsters . Cancer Res. , 38 , 4634 – 4639 ( 1978. ). [PubMed] [Google Scholar]
  • 11. ) Thamavit , W. , Kongkanuntn , R. , Tiwawech , D. and Moore , M. A.Level of Opisthorchis infestation and carcinogen dose dependence of cholangiocarcinoma induction in Syrian golden hamsters . Virchow Arch. B Cell Pathol. , 54 , 52 – 58 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Bunnag , D. and Harinasuta , T.Studies on the chemotherapy of human opisthorchiasis: I. Clinical trial of praziquantel . Southeast Asian J. Trop. Med. Public Health , 11 , 528 – 531 ( 1980. ). [PubMed] [Google Scholar]
  • 13. ) Thamavit , W. , Moore , M. A. , Sirisinha , S. , Shirai , T. and Ito , N.Time‐dependent modulation of liver lesion development in Opisthorchis‐infected Syrian hamsters by an antihelminthic drug, praziquantel . Jpn. J. Cancer Res. , 84 , 135 – 138 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Gordon , G. B. , Shantz , L. M. and Talalay , P.Modulation of growth, differentiation, and carcinogenesis by dehydroepiandrosterone . Adv. Enzyme Reg. , 26 , 355 – 382 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Ito , N. , Hirose , M. , Fukushima , S. , Tsuda , H. , Shirai , T. and Tatematsu , M.Studies on antioxidants; their carcinogenic and modifying effects on chemical carcinogenesis . Food Chem. Toxicol. , 24 , 1071 – 1082 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Rao , M. S. , Subbarao , V. , Kumar , S. , Yeldandi , A. V. and Reddy , J. K.Phenotypic properties of liver tumors induced by dehydroepiandrosterone in F‐344 rats . Jpn. J. Cancer Res. , 83 , 1179 – 1183 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Thamavit , W. , Moore , M. A. , Ruchirawat , S. and Ito , N.Repeated exposure to Opisthorchis viverrini and treatment with the antihelminthic praziquantel lacks carcinogenic potential . Carcinogenesis , 13 , 309 – 311 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Moore , M. A. , Tsuda , H. , Thamavit , W. , Masui , T. and Ito , N.Differential modification of development of preneoplastic lesions in the Syrian golden hamster initiated with a single dose of 2,2′‐dioxo‐N‐nitrosodipropylamine: influence of subsequent butylated hydroxyanisole, alpha‐tocopherol, or carbazole . J. Natl. Cancer Inst. , 78 , 289 – 293 ( 1987. ). [PubMed] [Google Scholar]
  • 19. ) The Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study Group . The effects of vitamin E and beta‐carotene on the incidence of lung cancer and other cancers in male smokers . N. Engl. J. Med. , 330 , 1029 – 1035 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Weber , E. , Moore , M. A. and Bannasch , P.Phenotypic modulation of hepatocarcinogenesis and reduction in N‐nitrosomorpholine‐induced hemangiosarcoma and adrenal lesion development in Sprague‐Dawley rats by dehydroepiandrosterone . Carcinogenesis , 9 , 1191 – 1196 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Moore , M. A. , Thamavit , W. , Tsuda , H. , Sato , K. , Ichihara , A. and Ito , N.Modifying influence of dehydroepiandrosterone on the development of dihydroxy‐di‐n‐propylnitrosamine initiated lesions in the thyroid and liver of F344 rats . Carcinogenesis , 7 , 311 – 316 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Schwartz , A. G. , Whitcomb , J. M. , Nyce , J. W. , Lewbart , M. L and Pashko , L. L.Dehydroepiandrosterone and structural analogs: a new class of chemopreventive agents . Adv. Cancer Res. , 51 , 391 – 424 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Garcea , R. , Daino , L. , Pascale , R. , Frassetto , S. , Cozzolino , O. P. , Ruggiu , M. E. , Vannini , M. G. , Pascale , R. , Lenzerini , L. , Simile , M. M. , Puddu , M. and Feo , F.Reversal by ribo‐ and deoxyribonucleosides of dehydroepiandrosterone‐induced inhibition of enzyme altered foci in the liver of rats subjected to the initiation‐selection process of experimental carcinogenesis . Carcinogenesis , 9 , 931 – 938 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Mayer , D. , Weber , E. , Moore , M. A. , Letsch , I. , Filsinger , E. and Bannasch , P.Dehydroepiandrosterone induced enzyme alterations in rat liver carbohydrate metabolism . Carcinogenesis , 9 , 2039 – 2043 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Sakuma , M. , Yamada , J. and Suga , T.Comparison of the inducing effect of dehydroepiandrosterone on hepatic peroxisome proliferation‐associated enzymes in several rodent species . Biochem. Pharmacol. , 43 , 1269 – 1273 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Moore , M. A. , Weber , E. and Bannasch , P.Modulating influence of dehydroepiandrosterone administration on the morphology and enzyme phenotype of dimethylamino‐azobenzene‐induced hepatocellular foci and nodules . Virchow Arch. B Cell Pathol. , 55 , 337 – 343 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Weber , E. , Moore , M. A. and Bannasch , P.Enzyme histochemical and morphological phenotype of amphophilic foci and amphophilic/tigroid cell neoplastic nodules in rat liver after combined treatment with dehydroepiandrosterone and N‐nitrosomorpholine . Carcinogenesis , 9 , 1049 – 1054 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Pashko , L. L. , Schwartz , A. G. , Abou‐Garbia , M. and Swern , D.Inhibition of DNA synthesis in mouse epidermis and breast epithelium by dehydroepiandrosterone and related steroids . Carcinogenesis , 2 , 717 – 721 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Andrade , Z. A. and Grimaud , J. A.Evolution of schistosomal hepatic lesions in mice after curative chemotherapy . Am. J. Pathol. , 124 , 59 – 65 ( 1986. ). [PMC free article] [PubMed] [Google Scholar]
  • 30. ) El‐Badrawy , N. M. , Botros , S. S. , Nagy , F. M. , Abdallah , N. M. and Herbage , D.Effect of praziquantel on hepatic fibrosis in experimental Schistosomiasis mansoni . Exp. Mol. Pathol. , 49 , 151 – 160 ( 1988. ). [DOI] [PubMed] [Google Scholar]

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