Carcinogenicity of cyproterone acetate in mouse

The synthetic progestin cyproterone acetate (CPA) has been shown to be a hepatocarcinogen in the rat, but little is known of its effects in mice. A 52 week CPA study in the mouse strain C57Bl/10J has been reported not to produce liver tumours, although CPA induced significant liver enlargement and i...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1996-07, Vol.17 (7), p.1473-1476
Main Authors: TUCKER, M. J, KALINOWSKI, A. E, ORTON, T. C
Format: Article
Language:English
Subjects:
Adenomatous Polyps - chemically induced
Adenomatous Polyps - pathology
Animals
Biological and medical sciences
Carcinogens - toxicity
Cyproterone Acetate - toxicity
Drug toxicity and drugs side effects treatment
Female
Hyperplasia
Islets of Langerhans - drug effects
Islets of Langerhans - pathology
Liver - drug effects
Liver - pathology
Liver Neoplasms, Experimental - chemically induced
Liver Neoplasms, Experimental - pathology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Miscellaneous (drug allergy, mutagens, teratogens...)
Organ Size - drug effects
Pharmacology. Drug treatments
Rats
Sex Characteristics
Species Specificity
Stomach Neoplasms - chemically induced
Stomach Neoplasms - pathology
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Summary:The synthetic progestin cyproterone acetate (CPA) has been shown to be a hepatocarcinogen in the rat, but little is known of its effects in mice. A 52 week CPA study in the mouse strain C57Bl/10J has been reported not to produce liver tumours, although CPA induced significant liver enlargement and induction of the mixed function oxidase CYP3A. The present study is a further investigation of the effects of CPA in mice of the C57Bl/10J strain dosed for 104 weeks. A group of 40 mice/sex were fed 800 p.p.m. CPA in the diet for 104 weeks with a control group of eight/sex. Mortality was high in females after 40 weeks due to hormonal effects in the uterus; no female and only four CPA-dosed males survived to 104 weeks. Liver cell hypertrophy with increased fat and glycogen and single cell or small multifocal areas of hepatocellular necrosis were universal. Proliferating cell nuclear antigen demonstrated an increase in proliferating cells within tumours and within the non-tumour bearing liver of CPA-dosed mice compared with normal livers of control mice. Hepatocellular tumours developed in 44% of males and 22% of females dosed with CPA, compared with none in the controls (the strain has a low,
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/17.7.1473