Genotoxic effects of 2-acetylaminofluorene on rat and human hepatocytes.

Abstract:

:Isolated rat and human hepatocytes in primary culture were shown to metabolize AAF to reactive intermediates which damaged hepatocyte DNA. A significant increase in unscheduled DNA synthesis was detectable by autoradiography in rat and human hepatocytes exposed to concentrations of AAF as low as 1 microM. When rat hepatocytes were plated over confluent monolayers of human fibroblasts and exposed to 3H-AAF, significant binding of AAF to the DNA of the fibroblasts as well as the hepatocytes was measured. In other experiments with hepatocyte-fibroblast cocultures, nonradioactive AAF, at concentrations greater than 40 microM, induced a significant increase in the HPRT- mutation frequency in the human fibroblasts. These results demonstrate that hepatocytes can be used to assess genotoxicity of carcinogenic compounds and are useful for interspecies comparisons in chemical carcinogenesis.

authors

Strom SC,Jirtle RL,Michalopoulos G

doi

10.1289/ehp.8349165

subject

Has Abstract

pub_date

1983-03-01 00:00:00

pages

165-70

eissn

0091-6765

issn

1552-9924

journal_volume

49

pub_type

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