Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1989 Jun;80(6):526–530. doi: 10.1111/j.1349-7006.1989.tb01671.x

Enhancing Effect of Ethanol on Aflatoxin B1‐induced Hepatocarcinogenesis in Male ACI/N Rats

Takuji Tanaka 1,✉, Akiyoshi Nishikawa 1, Hitoshi Iwata 1, Yoshio Mori 1, Akira Kara 1, Iwao Hirono 2, Hideki Mori 1
PMCID: PMC5917800  PMID: 2474524

Abstract

The modifying effect of ethanol (EtOH) on aflatoxin B1 (AFB1)‐induced hepatocarcinogenesis was examined in male ACI/N rats by chronic treatment at the post‐initiation phase. Rats received an ip injection of AFB1 (1.5 mg/kg) twice a week for 10 weeks (a total of 20 doses). Following a week of acclimation, they were given 10% EtOH as drinking water for 56 weeks. The effect of EtOH on the hepatocarcinogenesis was evaluated in terms of the incidence of altered hepatocellular foci and neoplasms at the end of the experiment. Exposure to AFB1 alone induced a substantial number of altered foci (6.98 iron‐excluding foci/cm2) in rats. The number of altered liver cell foci in rats receiving AFB1 followed by EtOH was significantly increased (26.39 iron‐excluding foci/cm2). In the rats given EtOH after AFB1 the total area and mean diameter of both iron‐excluding foci and altered foci identified in hematoxylin and eosin‐stained sections were significantly higher than in the rats exposed to AFB1 alone. The incidence of liver cell tumors of the group given AFB, and EtOH (3/15, 20%) was higher than that of the group treated with AFB1 alone (0/14, 0%). Treatment with EtOH alone for 56 weeks did not induce either. These results indicate an enhancing effect of EtOH on AFB1‐induced hepatocarcinogenesis when it is given in the promotion phase.

Keywords: Enhancing effect, Ethanol, Hepatocarcinogenesis, Aflatoxin b1—Rats

Full Text

The Full Text of this article is available as a PDF (308.2 KB).

REFERENCES

  • 1. ) Lieber , C. S. , Seitz , H. K. , Garro , A. J. and Worner , T. M.Alcohol‐related diseases and carcinogenesis . Cancer Res. , 39 , 2863 – 2886 ( 1979. ). [PubMed] [Google Scholar]
  • 2. ) Lieber , C. S. , Garro , A. , Leo , M. A. , Mak , K. M. and Worner , T.Alcohol and cancer , Hepatotogy , 6 , 1005 – 1019 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Driver , H. E. and Swann , P. F.Alcohol and human cancer (review) . Anticancer Res. , 2 , 309 – 320 ( 1987. ). [PubMed] [Google Scholar]
  • 4. ) Schmähl , D. , Thomas , C. , Sattler , W. and Scheld , G.Experimentelle Untersuchungen zur Syncarcinogenese. 3. Mitteilung: Versuche zur Krebserzeugung bei Ratten bei gleichzeitiger Gabe von Diäthylnitrosamine und Tetra‐chlorkohlenstoff bzw. Äthylalkohol, zugleich ein experhnenteller Beitrag zur Frage der “Alkoholcirrhose. ” Z. Krebsforsch. , 66 , 526 – 532 ( 1965. ). [Google Scholar]
  • 5. ) McCoy , G. D. , Hecht , S. S. and Katayama , S.Differential effect of chronic ethanol consumption on the carcinogenicity of N‐nitrosopyrrolidine and N'‐nitrosonornicotine in male Syrian golden hamsters . Cancer Res. , 41 , 2849 – 2854 ( 1981. ). [PubMed] [Google Scholar]
  • 6. ) Schottenfeld , D.Alcohol as a co‐factor in the etiology of cancer . Cancer , 43 , 1962 – 1966 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Radike , M. J. , Stemmer , K. L. , Brown , P. G. , Larson , E. and Bingham , E.Effect of ethanol and vinyl chloride on the induction of liver tumors: preliminary report . Environ. Health Perspect. , 21 , 153 – 155 ( 1977. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Griciute , L. , Castegnaro , M. and Bereziat , J‐C.Influence of ethyl alcohol on carcinogenesis with N‐nitrosodimethylamine . Cancer Lett. , 13 , 345 – 352 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Habs , M. and Schmähl , D.Inhibition of the carcinogenic activity of diethylnitrosamine (DENA) by ethanol in rats . Hepatogastroenterology , 28 , 242 – 244 ( 1981. ). [PubMed] [Google Scholar]
  • 10. ) Radike , M. J. , Stemmer , K. L. and Bingham , E.Effect of ethanol on vinyl chloride carcinogenesis . Environ. Health Perspect. , 41 , 59 – 62 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. ) Schwarz , M. , Buchmann , A. , Wiesbeck , G. and Kunz , W.Effect of ethanol on early stages in nitrosamine carcinogenesis in rat liver . Cancer Lett. , 20 , 305 – 312 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Teschke , R. , Minzlaff , M. , Oldiges , H. and Frenzel , H.Effect of chronic alcohol consumption on tumor incidence due to dimethylnitrosamine administration . J. Cancer Res. Clin. Oncol , 106 , 58 – 64 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Misslbeck , N.G. , Campbell , T. C. and Roe , D. A.Effect of ethanol consumed in combination with high or low fat diets on the postinitiation phase of hepatocarcinogenesis in the rat . J. Nutr. , 114 , 2311 – 2323 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Takada , A. , Nei , J. , Takase , S. and Matsuda , Y.Effects of ethanol on experimental hepatocarcinogenesis . Hepatology , 6 , 65 – 72 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Ikawa , E. , Tsuda , H. , Sakata , T. , Masui , T. , Satoh , K. , Sato , K. and Ito , N.Modification potential of ethyl alcohol and acetaldehyde on development of preneoplastic glutathione S‐transferase P‐form‐positive liver cell foci initiated by diethylnitrosamine in the rat . Cancer Lett. , 31 , 53 – 60 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Busby , W. F. , Jr. and Wogan , G. N.Aflatoxins . In “ Chemical Carcinogens ,” ed. Searle C. E. , Vol. 2 , pp. 945 – 1093 ( 1984. ). American Chemical Society; , Washington , D. C. [Google Scholar]
  • 17. ) IARC. “ Aflatoxins,” IARC Monographs on the Evaluation of Carcinogenic Risks to Humans , suppl. 7 , pp. 83 – 87 ( 1987. ). IARC; , Lyon ). [PubMed] [Google Scholar]
  • 18. ) Williams , G. M. , Hirota , N. and Rice , J.The resistance of spontaneous mouse hepatocellular tumors to iron accumulation during rapid iron loading by parenteral administration and their transplantability . Am. J. Pathol , 94 , 65 – 74 ( 1979. ). [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Stewart , H. L. , Williams , G. M. , Keysser , C. H. , Lombard , L. S. and Montali , R. J.Histologic typing of liver tumors of the rat. Institute of Laboratory Animal Resources, National Research Council, National Academy of Sciences . J. Natl. Cancer Inst. , 64 , 177 – 207 ( 1980. ). [PubMed] [Google Scholar]
  • 20. ) Williams , G. M , and Yamamoto , R. S.Absence of stainable iron from preneoplastic and neoplastic lesions in rat liver with 8‐hydroxyquinoline‐induced siderosis . J. Natl, Cancer Inst. , 49 , 685 – 692 ( 1972. ). [PubMed] [Google Scholar]
  • 21. ) Williams , G. M.The pathogenesis of rat liver cancer caused by chemical carcinogens . Biochim. Biophys. Acta , 605 , 167 – 189 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Ohnishi , K. , Lida , S. , Iwama , S. , Goto , N. , Nomura , F. , Takashi , M. , Mishima , A. , Kono , K. , Kimura , K. , Musha , H. , Kotota , K. and Okuda , K.The effect of chronic habitual alcohol intake on the development of liver cirrhosis and hepatocellular carcinoma; relation to hepatitis B surface antigen carriage . Cancer , 49 , 672 – 677 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) French , S. W.The Mallory body: structure, composition, and pathogenesis . Hepatology , 1 , 76 – 83 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Capel , I. D. , Jenner , M. , Pinnock , M. H. and Williams , D. C.The effect of alcohol intake upon the hepatic microsomal carcinogen‐activation system . Oncology , 35 , 168 – 170 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Borenfreund , E. , Higgins , P. J. and Bendich , A.In vivo‐in vitro rat liver carcinogenesis: modification in protein synthesis and uItrastructure . Ann. N. Y. Acad. Sci. , 349 , 357 – 372 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Bloomer , J. R. , Waldmann , T. A. , McIntire , K. R. and Klatskin , G.α‐Fetoprotein in non‐neoplastic hepatic disorders . J. Am. Med., Assoc. , 233 , 38 – 41 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Obidoa , O. and Okolo , T. C.Effect of ethanol administration on the metabolism of aflatoxin B1 . Biochem. Med. , 22 , 145 – 148 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Toskulkao , C. and Glinsukon , T.Effect of ethanol on the in vivo covalent binding and in vitro metabolism of aflatoxin B1 in rats . Toxicol Lett. , 30 , 151 – 157 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Toskulkao , C. , Taycharpipranai , S. and Glinsukon , T.Enhanced hepatotoxicity of aflatoxin b1 by pretreatment of rats with ethanol . Res. Commun. Chem. Pathol Pharmacol , 36 , 477 – 491 ( 1982. ). [PubMed] [Google Scholar]
  • 30. ) Ishii , H. , Joly , J. G. and Lieber , C. S.Effect of ethanol on the amount and enzyme activities of hepatic rough and smooth microsomal membranes . Biochim. Biophys. Acta , 291 , 411 – 420 ( 1973. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Joly , J. G. , Ishii , H. , Teschke , R. , Hasumura , Y. and Lieber , C. S.Effect of chronic alcohol feeding on the activities and submicrosomal distribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH)‐cytochrome P‐450 reductase and the demethylase for aminopyrine and ethylmorphine . Biochem. Pharmacol. , 22 , 1532 – 1535 ( 1973. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Busby , W. F. , Jr. and Wogan , G. N. Aflatoxins . In “ Mycotoxins and N‐Nitroso Compounds: Environmental Risks ,” ed. Shank R. C. , Vol. II , pp. 4 – 68 ( 1981. ). CRC Press; , Boca Raton , FL ). [Google Scholar]
  • 33. ) International Commission for Protection against Environmental Mutagens and Carcinogens. Conclusions on the genotoxicity of alcohol and recommendations for further work . Mutat. Res. , 186 , 175 – 176 ( 1987. ). [PubMed] [Google Scholar]

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

RESOURCES