Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE × 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr. DBE × 2 received 75 mg DBE/kg at 0 and 24 hr. All rats underwent a two-thirds partial hepatectomy at 28-29 hr, a one-third partial hepatectomy at 90 days, and were given 0.05% phenobarbital in drinking water for 4 months beginning at 1 yr. DBE was given to the DBE × 2 group twice within 24 hr because the compound is a hepatocyte mitogen. At 90 days, no appreciable changes were evident in any group. At 16 months, the incidence of nodules in the DBE × 2 group (25 of 41) was double that of the DBE × 1 group (12 of 38) (p < 0.01) and triple that of the control group (6 of 34) (p < 0,0001). Both the DBE × 1 and the DBE × 2 groups had higher incidences of eosinophilic foci, and also higher numbers, larger sizes, and larger areas of γ-glutamyltranspeptidase-positive foci than the control group. These results demonstrate for the first time that hepatocyte foci and nodules are initiated by limited exposure of animals to DBE.
References
1.
1. Burek JD (1978). A morphology and experimental study of the age associated lesions in aging BN/Bi, WAG/Rij and (WAS x BN) F1 rats. In: Pathology of Aging Rats.CRC Press, Inc., West Palm Beach. F1, pp. 58–68.
2.
2. Craddock VM and Frei JV (1974). Induction of liver cell adenomata in the rat by a single treatment with N-methyl-N-nitrosourea given at various times after partial hepatectomy.Br J Cancer30: 503–511.
3.
3. Hanson DJ (1984). Agricultural use of ethylene dibromide halted.Chem Eng News62: 13–16.
4.
4. Hagerstrand I (1973). Enzyme histochemistry of the liver in extrahepatic biliary obstruction.Acta Pathol Microbiol Scand (A)87: 737–750.
5.
5. Hill DL, Shih T, Johnston TP, and Strucki RF (1978). Macromolecular binding and metabolism of the carcinogen 1,2-dibromoethane.Cancer Res38: 2438–2442.
6.
6. Hollander CF and Bentvelzen P (1967). Enhancement of urethane induction of hepatomas in mice by prior partial hepatectomy.J Natl Cancer Inst41: 1303–1306.
7.
7. Institute of Laboratory Animal Resources (1980). Histologic typing of liver tumors of the rat.J Natl Cancer Inst64: 179–206.
8.
8. Kalengayi MMR, Ronchi G, and Desmet VJ (1975). Histochemistry of γ-glutamyltranspeptidase in rat liver during aflatoxin B1-induced carcinogenesis.J Natl Cancer Inst55: 579–588.
9.
9. Kitagawa T, Imai F, and Sato K (1980). Re-elevation of δ-glutamyltranspeptidase activity in periportal hepatocytes of rats with age.Gan71: 362–366.
10.
10. Labuc GE and Archer MC (1982). Comparative tumor-initiating activities of N-nitrosomethylbenzylamine and N-nitrosodimethylamine in rat liver.Carcinogenesis3: 519–523.
11.
11. Lipsky MM, Hinton DE, Klaunig JE, Goldblatt PJ, and Trump BJ (1978). γ-Glutamyltranspeptidase in safrole-induced, presumptive premalignant mouse hepatocytes.Carcinogenesis1: 151–156.
12.
12. Milks MM, Wilt SR, Ali I, Pereira MA, and Couri D (1982). Dibromoethane effects on the induction of δ-glutamyltranspeptidase positive foci in rat liver.Arch Toxicol51: 27–35.
13.
13. Moslen MT (1983). Increased incidence of foci and nodules in the livers of rats given one or two doses of 1,2-dibromoethane (DBE) followed by stimuli for cell replication. Fed Proc42: 1378 (abstract).
14.
13a. Moslen MT (1983). PhD dissertation. University of Texas Medical Branch, Galveston, TX.
15.
14. Nachtomi E and Farber E (1978). Ethylene dibromide as a mitogcn for liver.Lab Invest38: 279–283.
16.
15. Nachtomi E and Sarma DSR (1977). Repair of rat liver DNA in vivo damaged by ethylene dibromide.Biochem Pharmacol26: 1941–1945.
17.
16. Nadell J and Kosek J (1977). Peliosis hepatis: twelve cases associated with oral androgen therapy.Arch Pathol Lab Med101: 405–410.
18.
17. NTP/NCE (1982). Carcinogenis Bioassays of 1,2-dibromoethane (CAS No. 106-93-4) in F344 rats and B6C3F1 Mice (Inhalation Study) TR 210. NIH Pub No 82-1766.
19.
18. Ogawa K, Onoe T, and Takeuchi M (1981). Spontaneous occurrence of δ-glutamyltranspeptidase-positive hepatocytic foci in 105-week-old Wistar and 72-week-old Fischer 344 male rats.J Natl Cancer Inst67: 407–412.
20.
19. Olson WA, Habermann RT, Weisburger EK, Ward JM, and Weisburger JH (1973). Induction of stomach cancer in rats and mice by halogenated aliphatic fumigants.J Natl Cancer Inst51: 1993–1995.
21.
20. Peraino C, Fry JM, and Staffeldt EF (1980). Effects of varying the onset and duration of exposure to phenobarbital on its enhancement of 2-acetylami-nofluorene-induced hepatic tumorigenesis.Cancer Res37: 3623–3627.
22.
21. Pitot HC, Goldsworthy T, Moran S, Sirica AE, and Weeks J (1982). Properties of incomplete carcinogens and promotors in hepatocarcinogenesis.Carcinogenesis7: 85–98.
23.
22. Pound AW and McGuire LJ (1978). Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats.Br J Cancer37: 585–594.
24.
23. Presta M, Aletti MG, and Ragnotti G (1980). Decrease of the activity of the mixed function oxidase system in regenerating rat liver: an alternative explanation.Biochem Biophys Res Commun95: 829–834.
25.
24. Rannug U (1980). Genotoxic effects of 1,2-dibromoethane and 1,2-dichloroethane.Mutat Res76: 269–295.
26.
25. Ronchi G and Desmet VJ (1973). Histochemical study of γ-glutamyltranspeptidase (GGT) in experimental intrahepatic and extrahepatic cholestasis.Beitr Pathol150: 316–321.
27.
26. Rossi L.Ravera M, Repetti G, and Santi L (1977). Long-term administration of DDT or phenobarbital-Na to Wistar Rats. Int J Cancer19:179–185.
28.
27. Rutenberg AM, Kim H, Fischbein JW, Hanker JS, Wasserkrug HL, and Eligman AM (1969). Histochemical and ultrastructural demonstration of δ-glutamyltranspeptidase activity.J Histochem Cytochem17:517–526
29.
28. Schulte-Hermann R, Timmermann-Trosiener I, and Schuppler J (1983). Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds.Cancer Res43: 839–844.
30.
29. Sher SP, Jensen RD, and Bokelman DL (1982). Spontaneous tumors in control F344 and Charles River-CD rats and Charles River-CD-1 and B6C3HF1 mice.Toxicol Lett11: 103–110.
31.
30. Solt D and Farber E (1976). New principle for the analysis of chemical carcinogenesis.Nature263: 701–703.
32.
31. Stout DL and Becker FF (1982). Occurrence of progressive DNA damage coincident with the appearance of foci or altered hepatocytes.Carcinogenesis3: 599–602.
33.
32. Stuchikova E, Juricova-Horakova M, and Deyl Z (1975). New aspects of the dietary effect of life prolongation in rodents. What is the role of obesity in aging.Exp Gerontol10:141–144
34.
33. Tsuda H, Lee G, and Farber E (1980). Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens.Cancer Res40: 1157–1164.
35.
34. Van Bladeren PJ, Breimer DD, Rotteveel-Smijs GMT, de Jong RAW, Buijs W, Van der Gen A. and Mohn GR (1980). The role of glutathione conjugation in the mutagenicity of 1,2-dibromoethane.Biochem Pharmacol29: 2975–2982.
36.
35. Van Duuren BL, Goldschmidt BM, Lowengart G, Smith AC, Melchionne S, Seldman I, and Roth D (1979). Carcinogenicity of halogenated olefinic and aliphatic hydrocarbons in mice.J Natl Cancer Inst63: 1433–1439.
37.
36. Warwick GP (1971). Effect of the cell cycle on carcinogenesis.Fed Proc30:1760–1765
38.
37. Weibel ER (1969). Stereological principles for morphometry. Int Rev Cytol26: 235–302.
39.
38. Weisburger EK (1977). Carcinogenicity studies on halogenated hydrocarbons.Environ Health Perspect21: 7–16.
40.
39. Wong LCK, Wintons JM.Hong CB, and Plotnick H (1982). Carcinogenicity and toxicity of 1,2-dibromoethane in the rat.Toxicol Appl Pharmacol63: 155–165.
41.
40. Yager JD, Jr and Yager R (1980). Oral contraceptive steroids as promotors of hepatocarcinogenesis in female Sprague-Dawley rats.Cancer Res40: 3680–3685.
