Effects of the hepatocarcinogen 2-acetylaminofluorene on insulin binding to microsomal and Golgi fractions of rat liver cells.
Adult male Fischer rats fed the hepatocarcinogen 2-acetylaminofluorene [(2-AAF) CAS: 53-96-3; N-fluoren-2-yl-acetamide] at 0.02% showed a sharp decrease in the insulin binding to the Golgi fraction of the liver cells: from 10.0% specific binding per 0.1 mg protein in control animals to 5.9% after only 2 days and to 1.5% after 21 days of feeding 2-AAF. A less pronounced and slower decrease was observed in the microsomal fraction: from 19.1% specific binding per 0.5 mg protein in controls to a nadir of 10.8% after 46 days. The low binding of insulin to both fractions was observed for the 85 days of the experiment and persisted also in the animals fed 2-AAF for 90-107 days and then taken off the carcinogen for 30-75 days. The decrease in binding was due to the apparent decrease in the number of receptors. Neither 2-AAF nor its metabolites N-hydroxy-2-AAF (CAS: 53-95-2; N-fluoren-2-yl-acetohydroxamic acid) and N-acetoxy-2-AAF (CAS: 6098-44-8; N,O-diacetyl-N-fluoren-2-yl-hydroxylamine) influenced the insulin binding to the microsomes when added to the reaction mixture in vitro.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism*; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; C008147:insulin, iodo-; D015073:2-Acetylaminofluorene; D011972:Receptor, Insulin