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. 2008 Jun 28;30(1):1–5. doi: 10.1046/j.1365-2184.1997.00063.x

Dehydroepiandrosterone inhibits DNA synthesis of rat hepatocytes induced by partial hepatectomy or mitogen (ciprofibrate)

M S Rao 1,✉, V Subbarao 1
PMCID: PMC7081163  PMID: 9332491

Abstract

In a previous study we have shown that dehydroepiandrosterone (DHEA) inhibits hepatocyte DNA synthesis after short‐term administration and induces hepatocellular carcinomas after long‐term administration in the rat. It is not known whether DHEA is also capable of inhibiting replicative and mitogen‐induced DNA synthesis. In the present study, we have evaluated the effect of DHEA on DNA synthesis in the rat liver after partial hepatectomy and mitogen administration. After partial hepatectomy, DHEA significantly inhibited DNA synthesis at 20, 26, 32 and 38 h. Similarly, combined administration of ciprofibrate, a peroxisome proliferator and mitogen, and DHEA also resulted in significant hepatocyte DNA synthesis. However, DHEA did not affect liver enlargement caused by ciprofibrate. This experimental system will serve as useful tool to evaluate the role of cell proliferation in carcinogenesis.

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REFERENCES

  1. Ames BN, Gold IS. (1990) Too many rodent carcinogens: mitogenesis increases mutagenesis. Science 249, 970. [DOI] [PubMed] [Google Scholar]
  2. Bucher NLR. (1995) Liver regeneration. Then and now Jirtle RL, ed. Liver Regeneration and Carcinogenesis, New York : Academic Press, 1. [Google Scholar]
  3. Bucher NLR, Swaffield MN, DiTroia JF. (1964) The influence of age upon incorporation of thymidine‐2‐C14 into the DNA at regenerating rat liver. Cancer Res. 24, 509. [PubMed] [Google Scholar]
  4. Farber E. (1991) Hepatocyte proliferation in stepwise development of experimental liver cell cancer. Dig. Dis. Sci. 36, 973. [DOI] [PubMed] [Google Scholar]
  5. Fausto N, Laird AD, Webber EM. (1995) Role of growth factors and cytokines in hepatic regeneration. FASEB J. 9, 1527. [DOI] [PubMed] [Google Scholar]
  6. Frenkel RA, Slaughter CA, Orth K et al. (1990) Peroxisome proliferation and induction of peroxisomal enzymes in mouse and rat liver by dehydroepiandrosterone feeding. J. Steroid. 35, 333. [DOI] [PubMed] [Google Scholar]
  7. Grisham JW. (1968) Cellular proliferation in the liver Fry RJM, Griem ML, Kirsten WH, eds. Recent Results in Cancer Research. Normal and Malignant Cell Growth. New York : Springer‐Verlag, 28. [Google Scholar]
  8. Hayashi F, Tamura H, Yamada, J , Kasai H, Suga T. (1994) Characteristics of hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F‐344 rats. Carcinogenesis 15, 2215. [DOI] [PubMed] [Google Scholar]
  9. Higgins GM, Anderson RM. (1931) Experimental pathology of liver. 1. Restoration of liver of white rat following partial surgical removal. Arch. Pathol. 12, 186. [Google Scholar]
  10. Ledda‐Columbano GM, Columbano A, Cannas A et al. (1994) Dexamethasone inhibits induction of liver tumor necrosis factor‐α mRNA and liver growth induced by lead nitrate and ethylene dibromide. Am. J. Pathol. 145, 951. [PMC free article] [PubMed] [Google Scholar]
  11. Moody DE. (1994) Peroxisome proliferation: an overview Moody DE, ed. Peroxisome Proliferators. Unique Inducers of Drug‐metabolizing Enzymes. Boca Raton : CRC Press, 1. [Google Scholar]
  12. Nestler JE. (1995) DHEA: A coming of age. An. N. Y. Acad. Sci. 774, ix. [Google Scholar]
  13. Ohmura T, Ledda‐Columbano GM, Piga R et al. (1995) Hepatocyte proliferation induced by single dose of a peroxisome proliferator. Am. J. Pathol. 148, 185. [PMC free article] [PubMed] [Google Scholar]
  14. Rao MS, Reddy JK. (1991) Toxicological implications of peroxisome proliferation Meeks R, Harrison S, Bull R, eds. Hepatotoxicology. Boca Raton : CRC Press, 621. [Google Scholar]
  15. Rao MS, Reddy JK. (1997) Hepatocarcinogenesis of peroxisome proliferators. An. N. Y. Acad. Sci. 804, 573. [DOI] [PubMed] [Google Scholar]
  16. Rao MS, Subbarao V, Yeldandi AV, Reddy JK. (1992a) Hepatocarcinogenicity of dehydroepiandrosterone in the rat. Cancer Res. 52, 2977. [PubMed] [Google Scholar]
  17. Rao MS, Musunuri S, Reddy JK. (1992b) Dehydroepiandrosterone induced peroxisome proliferation in the rat liver. Pathobiol. 60, 82. [DOI] [PubMed] [Google Scholar]
  18. Reddy JK, Lalwani ND. (1983) Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. CRC Rev. Toxicol. 12, 1. [DOI] [PubMed] [Google Scholar]
  19. Schwartz AG, Pashko LL. (1995) Mechanism of cancer preventive action of DHEA. An. N. Y. Acad. Sci. 774, 180. [DOI] [PubMed] [Google Scholar]
  20. Schwartz AG, Whitcomb JM, Nyce JW, Lewbart ML, Pashko LL. (1988) Dehydroepiandrosterone and structural analogs. A new class of cancer chemopreventive agents. Ad. Cancer Res. 51, 391. [DOI] [PubMed] [Google Scholar]
  21. Shinozuka H, Kubo Y, Katyal YS et al. (1994) Roles of growth factors and tumor necrosis factor‐α on liver cell proliferation induced in rats by lead nitrate. Lab. Invest. 71, 35. [PubMed] [Google Scholar]

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