Inbred male Leeds strain rats were given a diet containing 0.05% N-fluoren-4-ylacetohydroxamic acid for up to 7 months. A modified method for the synthesis of this compound is described. Rats were killed at intervals during and after treatment and their liver tissues examined by light and electron microscopy. The treated rats developed a very low incidence of (non-hepatic) tumours and hepatic clear cell foci appeared during the late stages of the experiment. The only significant fine structural changes observed were glycogenosis and alterations in the morphology of the rough endoplasmic reticulum, both of which developed only after prolonged treatment and affected a minority of hepatocytes. These changes are discussed in relation to the fine structural changes elicited by the strongly carcinogenic N-fluoren-2-ylacetamide and the non-carcinogen, N-fluoren-4-ylacetamide.
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http://dx.doi.org/10.1093/carcin/3.1.103 | DOI Listing |
Chem Res Toxicol
December 2009
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, Minnesota 55455, USA.
Human arylamine N-acetyltransferases (NATs) are expressed as two polymorphic isoforms, NAT1 and NAT2, that have toxicologically significant functions in the detoxification of xenobiotic arylamines by N-acetylation and in the bioactivation of N-arylhydroxylamines by O-acetylation. NAT1 also catalyzes the N-acetylation of 4-aminobenzoylglutamic acid, a product of folic acid degradation, and is associated with endogenous functions in embryonic development. On the basis of earlier studies with hamster NAT1, hamster NAT2, and human NAT1, we proposed that human NAT2 would be more susceptible than NAT1 to inactivation by N-arylhydroxamic acid metabolites of arylamines.
View Article and Find Full Text PDFInbred male Leeds strain rats were given a diet containing 0.05% N-fluoren-4-ylacetohydroxamic acid for up to 7 months. A modified method for the synthesis of this compound is described.
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