0000000000133006
AUTHOR
M. Metzler
Metabolites of diethylstilboestrol induce sister chromatid exchange in human cultured fibroblasts
Diethylstilboesterol (DES) is one of the few substances for which a clear association with carcinogenicity has been established in man. Nevertheless, it is still widely used, mainly as a cheap oestrogen to increase the slaughter weight of beef, but in spite of this it is not known if residues in the meat or metabolites excreted by the cattle are hazardous to man. It is also unknown whether there is a threshold dose below which DES is harmless. A threshold might be expected if a hormonal mechanism of carcinogensis rather than metabolic activation to an electrophically reactive species operats. This possibility was supported by the observations that DES, in contrast to most other carcinogens,…
Metabolic epoxidation of trans-4-acetylaminostilbene: A protective mechanism against its activation to a mutagen
Abstract Trans -4-acetylaminostilbene is activated by liver preparations to mutagens for Salmonella typhimurium . Since this compound is metabolized to the trans -α,β-epoxide and since many epoxides are ultimate mutagens, this epoxide was tested for direct mutagenicity. It was, however, found to be non-mutagenic, and, in contrast to the parent compound, the epoxide was no longer activated by liver preparations to mutagens. The same was found for the β-ketone and for the threo -α,β-dihydrodiol, which are formed metabolically from trans -4-acetylaminostilbene and from its α,β-epoxide. 4-Acetylaminobibenzyl showed a very weak mutagenic activity in the presence of the liver preparation. Thus, i…