Strain Differences in Susceptibility to 2-Acetylaminofluorene and Phenobarbital Promotion of Rat Hepatocarcinogenesis in a Medium-term Assay System: Quantitation of GlutathioneS-Transferase P-positive Foci Development

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Abstract
Strain differences in susceptibility to promotion by the liver carcinogens 2‐acetylaminofluorene (2‐AAF) and phenobarbital (PB) were examined in the medium‐term bioassay system initially developed in our laboratory using male F344 rats as the test animal and glutathione S‐transferase placental form (GST‐P)‐positive foci as the lesion end‐point. Numbers and areas per cm2 of induced GST‐P‐positive hepatocellular foci were compared in LEW, F344, NAR, SD, WBN, SHR, Wistar and ODS rats initiated with diethylnitrosamine (DEN) and subjected to partial hepatectomy during subsequent administration of 2‐AAF or PB. LEW, SD, WBN, and F344 rats were most susceptible to hepatopromotion by both compounds, with a hundred fold increase in lesion area being observed for 2‐AAF in the LEW case. NAR and SHR strains demonstrated an intermediate response, while Wistar and, in particular, the related ODS rats demonstrated very low susceptibilities. The obvious strain differences could be expressed in terms of comparative indices of promoting effects of 2‐AAF and PB as well as DEN itself regarding each of the 8 strains tested. The use of F344 rats for the bioassay model was validated by the relatively high sensitivity to both DEN and 2‐AAF initiation as well as second‐stage promotion stimulus exhibited.