Female Sprague-Dawley rats were partially hepatectomized, initiated with diethylnitrosamine (DEN), and fed diets containing 2,2′,4,4′,5,5′-hexabromobiphenyl (245-HBB), 3,3′,4,4′,5,5′-hexachlorobiphenyl (345-HCB), or combinations of 245-HBB and 345-HCB to determine the tumor-promoting ability of these compounds in a two-stage (initiation/promotion) hepatocar-cinogenesis system. Tumor-promoting ability was assessed by measuring hepatic foci positive for gamma glutamyl transpeptidase (GGT) activity. Concentrations of 10 or 100 mg 245-HBB/kg of diet caused significantly increased numbers of GGT-positive hepatic foci. When 245-HBB and 345-HCB were fed simultaneously, an additive effect on tumor-promoting ability was observed at dietary concentrations of 10 mg/kg 245-HBB and 0.1 mg/kg 345-HCB. However, an inhibitory effect on tumor promotion occurred when dietary concentrations of 100 mg/kg 245-HBB and 1.0 mg/kg 345-HCB were fed simultaneously. These results suggest that the tumor-promoting ability of simultaneous exposure to 245-HBB and 345-HCB can be additive or inhibitory depending upon the concentration of each congener in the diet.
References
1.
1. Tennant, R.W., Margolin, B.H., Shelby, M.D., Zeiger, E., Haseman, J.K., Spalding, J., Caspary, W., Resnick, M., Stasiewicz, S., Anderson, B., and Minor, R. (1987). Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays.Science236, 933–941.
2.
2. Jensen, R.K., Sleight, S.D., Goodman, S.D., Aust, S.D., and Trosko, J. E. (1982). Polybrominated biphenyls as promoters in experimental hepatocarcinogenesis in rats.Carcinogenesis3, 1183–1186.
3.
3. Jensen, R.K., and Sleight, S.D. (1986). Sequential study on the synergistic effects of 2. 2'. 4. 4'. 5. 5'-hexabromobiphenyl and 3, 3'. 4, 4'. 5. 5'-hexabromobiphenyl on hepatic tumor promotion. Carcinogenesis 7, 1771-1774.
4.
4. Moore, R.W., and Aust, S. D. (1978). Purification and structural characterization of polybrominated biphenyl congeners.Biochim. Biophys. Res. Commun.84, 936–942.
5.
5. Aust, S.D., Dannan, G.A., Sleight, S.D., Fraker, P.J., Ringer, R.K., and Polin, D. (1982). Toxicology of polybrominated biphenyls. In: Khan, M.A.Q. (ed.) Toxicology of Halogenated Hydrocarbons: Health and Ecological Effects. Elmsford. Ny: Pergamon Press pp. 73–96
6.
6. Rutenburg, A.M., Kim, H., Fischbein, L.W., Hanker, J.S., Wasserkrug, H.L., and Seligman, A. M. (1969). Histochemical and ultrastructural demonstration of gamma glutamyl transpeptidase activity.J. Histochem. Cytochem.17, 517–526.
7.
7. Scherer, E. (1981). Use of a programmable pocket calculator for the quantitation of precancerous foci.Carcinogenesis2, 805–807.
8.
8. Steel, R.G.D., and Torrie, J. H. (1980). Analysis of variance I: The one-way classification. In: Napier, C., and Maisel, J.W. (eds.) 1. New York: Mc Graw-Hill, pp. 137–191.
9.
9. Institute Of Laboratory Animal Resources, National Research Council, National Academy Of Sciences (1980). Histologic typing of liver tumors of the rat.J. Natl. Cancer Inst.64, 177–206.
10.
10. Pitot, H.C., Barsness, L., Goldsworthy, T., and Kitigawa, T. (1978). Biochemical characterization of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine.Nature271, 456–458.
11.
11. Leonard, T.B., Dent, J.G., Graichen, E., Lyght. O, and Popp, J. A. (1982). Comparison of hepatic carcinogen initiation-promotion systems.Carcinogenesis3, 851–856.
12.
12. Farber, E. (1984). Precancerous steps in carcinogenesis. Their physiological adaptive nature.Biochim. Biophys. Acta738, 171–180.
13.
13. Scherer, E. (1984). Neoplastic progression in experimental hepatocarcinogenesis.Biochim. Biophys. Acta738, 219–236.
14.
14. Schulte-Hermann, R. (1985). Tumor promotion in the liver.Arch. Toxicol.57, 147–158.
15.
15. Williams, G.M. (1982). Phenotypic properties of preneoplastic rat liver lesions and applications to detection of carcinogen and tumor promoters.Toxicol. Pathol.10, 3–11.
16.
16. Jensen, R.K., Sleight, S.D., Aust, S.D., Goodman, J.I., Trosko, J. E. (1983). Hepatic tumor promoting ability of 3, 3'. 4, 4'. 5, 5'-hexabromobiphenyl: The interrelationship between toxicity, induction of hepatic microsomal drug metabolizing enzymes and tumor-promoting ability.Toxicol. Appl. Pharmacol.71, 163–176.
17.
17. Pitot, H.C., Goldworthy, T., Campbell, H.A., and Poland, A. (1980). Quantitative evaluation of the promotion by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine.Cancer Res.40, 3616–3620.
18.
18. Pitot, H.C., and Sirica, A. E. (1980). The stages of initiation and promotion in hepatocarcinogenesis.Biochim. Biophys. Acta605, 191–215.
19.
19. Williams, G.M., Katayama, S., and Ohmori, T. (1981). Enhancement of hepatocarcinogenesis by sequential administration of chemicals: Summation versus promotion effects.Carcinogenesis2, 1111–1117.
20.
20. Garthoff, L.H., Friedman, L., Farber, T.M., Locke, K.K., Sobotka, T.J., Green, S., Hurley, N., Peters, E.L., Story, G.E., Moreland, F.M., Graham, C.H., Keys, J.E., Taylor, M.J., Scalera, J.V., Rothlein, J.E., Marks, E.M., Cerra, F.E., Rodi, S.B., and Sporn, E. M. (1977). Biochemical and cytogenetic effects in rats caused by short-term ingestion of Aroclor 1254 or Firemaster Bp-6.J. Toxicol. Environ. Health3, 769–796.
21.
21. Kimbrough, R.D., Groce, D.F., Korver, M.P., and Burse, V.W. (1981). Induction of liver tumors in female Sherman strain rats by polybrominated biphenyls.J. Natl. Cancer Inst.66, 535–542.
22.
22. Farber, E. (1984). The malignant phenotype as a late expression in the carcinogenetic process.J. Cell Physiol.3, 123–125, (Suppl).
23.
23. Goldsworthy, T.L., and Pitot, H. C. (1985). The quantitative analysis and stability of histochemical markers of altered hepatic foci in rat liver following initiation by diethylnitrosamine administration and promotion with phenobarbital.Carcinogenesis6, 1261–1269.
24.
24. Peraino, C., Staffeldt, E.F., Carnes, B.A., Ludeman, V.A., Blomquist, J.A., and Vesselinovitch, S. D. (1984). Characterization of histochemically detectable altered hepatocyte foci and their relationship to hepatic tumorigenesis in rats treated once with diethylnitrosamine or benzo[a]pyrene within one day after birth.Cancer Res.44, 3340–3347.
25.
25. Jensen, R.K. (1983). Pathologic effects and hepatic tumor promoting ability of Firemaster Bp-6. 3, 3', 4, 4', 5, 5'-hexabromobiphenyl, and 2,2', 4,4', 5, 5'-hexabromobiphenyl in the rat. Ph.D. Dissertation, Michigan State University.
26.
26. Tucker, M.J. (1979). The effect of long-term food restriction on tumors in rodents.Int. J. Cancer23, 803–807.
