PROMOTING ACTIVITIES OF THE C-9 OXIDIZED METABOLITES OF N-2-FLUORENYLACETAMIDE IN LIVER CARCINOGENESIS IN THE RAT

  • Authors:
    • P VIJAYARAGHAVAN
    • D MALEJKA-GIGANTI
    • H SHINOZUKA
  • View Affiliations

  • Published online on: August 1, 1995     https://doi.org/10.3892/ijo.7.2.287
  • Pages: 287-294
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Abstract

The promoting potential of the C-9 oxidized metabolites of N-2-fluorenylacetamide (2-FAA) was examined and compared to that of the promoter 2-FAA in the two-stage hepatocarcinogensis system Male Sprague Dawley rats were initiated with a single intraperitoneal injection of diethylnitrosamine at 200 mg/kg of body weight (b.wt.). One, 2 and 5 weeks thereafter rats were given by gavage 5 doses per week of 2-FAA (0.05 mmol/kg of b.wt.), 9-hydroxy- or 9-oxo-2-FAA (0.05 and 0.1 mmol/kg of b.wt.) or the vehicle polyethylene glycol 400 (2 ml/kg of b.wt.). All rats underwent partial (70%) hepatectomy on day 3 after 5 initial doses. Following treatment with 2FAA, 9-hydroxy-or 9-oxo-2-FAA, the levels of gamma-glutamyl-transpeptidase activity and placental glutathione S-transferase (GST-P) were increased in the livers proportional to the increased numbers of foci of GST-P positive hepatocytes. The activities of the C-9 oxidized compounds were dose-dependent since treatment at 0.1 mmol/kg of b.wt. resulted in -2-fold greater effects than that at 0.05 mmol/kg of b.wt. The incidences of hepatocellular carcinoma increased with time after treatment and the relative order of potency was: 2-FAA>9-oxo-2-FAA>9-hydroxy-2-FAA. These data combined with our earlier evidence for preferential oxidations of 2-FAA at C-9 by hepatic microsomes of male Sprague Dawley rats support the significance of these metabolites as a promoting stimuli in liver carcinogenesis by 2-FAA.

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August 1995
Volume 7 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
VIJAYARAGHAVAN P, MALEJKA-GIGANTI D and SHINOZUKA H: PROMOTING ACTIVITIES OF THE C-9 OXIDIZED METABOLITES OF N-2-FLUORENYLACETAMIDE IN LIVER CARCINOGENESIS IN THE RAT. Int J Oncol 7: 287-294, 1995
APA
VIJAYARAGHAVAN, P., MALEJKA-GIGANTI, D., & SHINOZUKA, H. (1995). PROMOTING ACTIVITIES OF THE C-9 OXIDIZED METABOLITES OF N-2-FLUORENYLACETAMIDE IN LIVER CARCINOGENESIS IN THE RAT. International Journal of Oncology, 7, 287-294. https://doi.org/10.3892/ijo.7.2.287
MLA
VIJAYARAGHAVAN, P., MALEJKA-GIGANTI, D., SHINOZUKA, H."PROMOTING ACTIVITIES OF THE C-9 OXIDIZED METABOLITES OF N-2-FLUORENYLACETAMIDE IN LIVER CARCINOGENESIS IN THE RAT". International Journal of Oncology 7.2 (1995): 287-294.
Chicago
VIJAYARAGHAVAN, P., MALEJKA-GIGANTI, D., SHINOZUKA, H."PROMOTING ACTIVITIES OF THE C-9 OXIDIZED METABOLITES OF N-2-FLUORENYLACETAMIDE IN LIVER CARCINOGENESIS IN THE RAT". International Journal of Oncology 7, no. 2 (1995): 287-294. https://doi.org/10.3892/ijo.7.2.287