Effects of cyproterone acetate in C57B1/10J mice.
Male and female C57BL/10J mice were fed 0 or 800 ppm cyproterone acetate (CPA) in the diet for 13 weeks. 1. Body weight was reduced (P > 0.001 at 13 weeks) by approximately 33%. 2. Seminal vesicle weights were reduced (P > 0.001) and showed histological atrophy, changes consistent with the anti-androgenic activity of the compound. 3. Liver weights were increased (P > 0.001) by +90% of control mean weights; hepatocyte hypertrophy and increased fat and glycogen were seen by light microscopy, and hyperplasia of smooth endoplasmic reticulin by transmission electron microscopy. 4. Assessment of liver mixed function oxidase activity demonstrated induction of cytochrome P450 enzymes, and increased isozyme 2B1/2 in males and 3A1 in both sexes was confirmed by immunohistochemical staining of liver sections. 5. An increase in bromodeoxyuridine (BrdU) labelling index of the liver was seen in females only. 6. This study is the first in a programme of work with CPA designed to investigate the effects of the compound in mice. It demonstrates that the hepatic effects of the compound which have been described in the rat also occur in mice.
Tucker
M J
MJ
Safety of Medicines Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Jones
D V
DV
D000726:Androgen Antagonists / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000633:toxicity; D017373:Cyproterone Acetate / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats
D000726:Androgen Antagonists; D000963:Antimetabolites; D017373:Cyproterone Acetate; D006899:Mixed Function Oxygenases; D001973:Bromodeoxyuridine