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Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene.

Publication ,  Journal Article
Rudo, K; Meyers, WC; Dauterman, W; Langenbach, R
Published in: Cancer Res
November 15, 1987

A method has been developed to assess the metabolism and mutagenic activation of carcinogens using human and rodent hepatocytes in vitro. A slicing technique which was especially useful for nonperfusable biopsy and resected surgical human liver tissue was used to prepare the hepatocytes. Metabolites of the model carcinogen 2-acetylaminofluorene (AAF) produced by human and rat hepatocytes were similar and consisted primarily of 2-aminofluorene with ring hydroxylated products at the 1-, 3-, 5/9-, 7-, and 8-positions produced in addition to N-hydroxy-AAF. Sulphate and glucuronide conjugates of ring-hydroxylated metabolites and 2-aminofluorene were detected. Metabolism and cell-mediated Salmonella mutagenicity illustrated interindividual variation with human hepatocytes. Levels of metabolism and mutagenesis were generally higher with human hepatocytes compared to rat hepatocyte results. The increased levels of metabolism and mutagenesis of AAF by human hepatocytes compared to rat hepatocytes probably indicates a different sensitivity to hepatocarcinogenic effects of AAF on humans as compared to rats. Understanding differences and similarities between human and rodent carcinogen activation capabilities should be useful in the extrapolation of rodent carcinogenesis data to humans.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

November 15, 1987

Volume

47

Issue

22

Start / End Page

5861 / 5867

Location

United States

Related Subject Headings

  • Species Specificity
  • Salmonella typhimurium
  • Rats
  • Oncology & Carcinogenesis
  • Mutation
  • Mutagens
  • Mutagenicity Tests
  • Male
  • Liver Neoplasms
  • Liver
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rudo, K., Meyers, W. C., Dauterman, W., & Langenbach, R. (1987). Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene. Cancer Res, 47(22), 5861–5867.
Rudo, K., W. C. Meyers, W. Dauterman, and R. Langenbach. “Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene.Cancer Res 47, no. 22 (November 15, 1987): 5861–67.
Rudo K, Meyers WC, Dauterman W, Langenbach R. Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene. Cancer Res. 1987 Nov 15;47(22):5861–7.
Rudo, K., et al. “Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene.Cancer Res, vol. 47, no. 22, Nov. 1987, pp. 5861–67.
Rudo K, Meyers WC, Dauterman W, Langenbach R. Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene. Cancer Res. 1987 Nov 15;47(22):5861–5867.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

November 15, 1987

Volume

47

Issue

22

Start / End Page

5861 / 5867

Location

United States

Related Subject Headings

  • Species Specificity
  • Salmonella typhimurium
  • Rats
  • Oncology & Carcinogenesis
  • Mutation
  • Mutagens
  • Mutagenicity Tests
  • Male
  • Liver Neoplasms
  • Liver