Heterogenous rabbit antisera were prepared against microsomal proteins of hyperplastic hepatic nodules (HPN) induced by chemicals, and were utilized to assess the antigenic differences of microsomal polypeptides within a normal liver, HPN, and hepatocellular carcinomas (HCC), utilizing immunodetection of antigens separated electrophoretically and transferred to nitrocellulose. Although most antigens were common to all microsomes, differences (increase or decrease) were noted in some polypeptides not only between the normal liver and HPN, but also between HPN and HCC. On the other hand, monoclonal antibodies against epoxide hydrolase (EH), which was initially found as the PN antigen, reacted to a single polypeptide with a molecular weight of 49,000 in all the microsomes. These results suggested that there is little molecular modification of EH during hepatic carcinogenesis.
References
1.
1. Astrom A, DePierre JW, and Erriksson L (1983). Characterization of drug-metabolizing systems in hyperplastic hepatic nodules from the livers of rats receiving 2-acetylaminofluorene in their diet. Carcinogenesis4:577–581.
2.
2. Bannasch P, Mayer D, and Hecker HJ (1980). Hepatocellular glycogenesis and hepatocarcinogenesis. Biochim. Biophys. Acta605:217–245.
3.
3. Buchmann A, Kuhlmann W, Schwartz M, Kunz W, Wolf CR, Moll E, Friedberg T, and Oesch F(1985). Regulation and expression of four cytochrome P-450 isoenzymes. NADPH-cytochrome P-450 reductase, the glutathione transferase B and C and microsomal epoxide hydrolase in preneoplastic and neoplastic lesions in rat liver. Carcinogenesis6:513–521.
4.
4. Emmelot P and Scherer E (1980). The first relevant cell stage in rat liver carcinogenesis. Biochim. Biophys. Acta605:247–304.
5.
5. Eriksson LC, Torndal UB, and Anderson GN (1983). Isolation and characterization of endoplasmic reticulum and Golgi apparatus from hepatocyte nodules in male Wistar rats. Cancer Res.43:3335–3347.
6.
6. Farber E (1980). The sequential analysis of liver cancer induction. Biochim. Biophys. Acta605:149–166.
7.
7. Farber E, Parker S, and Gruenstein M (1976). The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens. Cancer Res.36:3879–3887.
8.
8. Franke WW, Mayer D, Schmid E, Denk H, and Borenfreund L (1981). Differences of expression of cytoskeletal proteins in cultured rat heptocytes and hepatoma cells. Exp. Cell Res.134:345–365.
9.
9. Griffin MJ and Kizer DE (1978). Purification and quantitation of preneoplastic antigen from hyperplastic nodules and normal liver. Cancer Res.38:1136–1141.
10.
10. Laemmli UK (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680–685.
11.
11. Levin W, Lu AYH, Thomas PE, Ryan D, Kizer DE, and Griffin MJ (1978). Identification of epoxide hydrolase as the preneoplastic antigen in rat liver hyperplastic nodules. Proc. Natl. Acad. Sci.75:3240–3243.
12.
12. Lin J-C, Kligman L, and Farber E (1980). Purification and partial characterization of a preneoplastic antigen in liver carcinogenesis. Cancer Res.40:3755–3762.
13.
13. Lu AYH and Levin W (1978). Purification and assay of liver microsomal epoxide hydrolase. Methods Enzymol.52:193–200.
14.
14. Merkow LP, Epstein SM, Farber E, Pardo M, and Bartus B (1971). Ultrastructural alterations within hyperplastic nodules and hepatocellular carcinomas induced in rat liver by ethionine. Cancer Res.31:174–177.
15.
15. Oesch F, Vogel-Bindel, U, Guenthner TH, Cameron R, and Farber E (1983). Characterization of microsomal epoxide hydrolase in hyperplastic liver nodules of rats. Cancer Res.43:313–319.
16.
16. Ogawa K, Medline A, and Farber E (1979). Sequential analysis of hepatic carcinogenesis. A comparative study of the ultrastructure of preneoplastic, malignant, perinatal and regenerating liver. Lab. Invest.41:22–35.
17.
17. Okita K and Farber E (1975). An antigen common to preneoplastic hepatocyte populations and liver cancer induced by N-2-fluorenylacetamide, ethionine, or other carcinogens. Gann Monogr.17:283–299.
18.
18. Raymondjean M, Defer N, Tichonicky L, Kruh J, Kreip B, and Gugiren-Guillouzo C (1983). Changes in poly(A)+RNA translational pattern during chemically induced hepatocarcinogenesis. Carcinogenesis6:1797–1803.
19.
19. Sato K, Kitahara A, Yin Z, Ebina T, Satoh K, Hatayama I, Nishimura K, Yamazaki T, Tsuda H, Ito N, and Dempo K (1983). Molecular forms of glutathione-S-transferase and UDP-glucuronyltransferase as hepatic preneoplastic marker enzymes. Ann. NY Acad. Sci.417:213–223.
20.
20. Scharma RN, Gurtoo HL, Farber E, Murray RK, and Cameron R (1981). Effects of hepatocarcinogens and hepatocarcinogenesis on the activity of rat liver microsomal epoxide hydrolase and observations on electrophoretic behavior of this enzyme. Cancer Res.41:3311–3319.
21.
21. Schmidt WN, Gronert BJ, Page DL, Briggs RC, and Hnilica LS (1982). Antigenic changes in nonhistone proteins during azo dye hepatocarcinogenesis. Cancer Res.42:3164–3174.
22.
22. Solt D and Farber E (1976). New principles for the analysis of chemical carcinogenesis. Natttre263:701–703.
23.
23. Sugioka Y, Fujii-Kuriyama, Y, Kitagawa T, and Muramatsu M (1985). Changes in polypeptide pattern of rat liver cells during chemical hepatocarcinogenesis. Cancer Res.45:365–378.
24.
24. Williams GM (1980). The pathogenesis of rat liver cancer caused by chemical carcinogens. Biochim. Biophys. Acta605:167–189.
25.
25. Wirth PJ, Benjamin T, Schwartz DM, and Thorgeirsson SS (1986). Sequential analysis of chemically induced hepatoma development in rats by two dimensional electrophoresis. Cancer Res.46:400–413.
