Prevalidation of a rat liver foci bioassay (RLFB) based on results from 1600 rats: a study report.

A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione-S-transferase (placental form, GSTP) and by staining with hematoxilin/eosin (H&E), and their area fraction was quantified morphometrically. The four model hepatocarcinogens N-nitrosomorpholine, 2-acetylaminofluoren, phenobarbital, and clofibrate were selected according to characteristic differences in their presumed mode of action, and tested in a total of 1,600 male and female rats at 2 different dose levels.

Diethylnitrosamine induces long-lasting re-expression of insulin-like growth factor II during early stages of liver carcinogenesis in mice.

The expression of the insulin-like growth factor II (IGF-II) gene (Igf2) in rodents is completely abrogated in almost all adult tissues. A prominent exception are neoplasms in which IGF-II frequently serves as an autocrine growth factor. We have investigated the potential role of Igf2 expression during liver carcinogenesis.

Dose dependent induction of DNA adducts, gene mutations, and cell proliferation by the antiandrogenic drug cyproterone acetate in rat liver.

1. CPA does not only induce the formation of DNA adducts but also of mutations in female rat liver. 2.

The DNA damaging drug cyproterone acetate causes gene mutations and induces glutathione-S-transferase P in the liver of female Big Blue transgenic F344 rats.

The gestagenic and antiandrogenic drug cyproterone acetate (CPA) is mitogenic, tumorigenic and induces DNA-adducts and DNA-repair synthesis in rat liver. Thus CPA is expected to be mutagenic. However in vitro mutagenicity test systems were negative.

Chlorinated dibenzodioxins and dibenzofurans (PCDD/F) in blood and human milk of non occupationally exposed persons living in the vicinity of a municipal waste incinerator.

The concentrations of chlorinated dibenzodioxins and dibenzofurans (PCDD/F) in human blood and in milk from non-occupationally exposed persons living in the vicinity of a municipal waste incinerator were determined. As compared to background levels in the general population in Germany the results give no indication of an enhanced body burden of PCDD/F. This is in agreement with earlier investigations in the same area, showing normal background concentrations in soil, fruit and vegetables.