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Oxymetholone: III. Evaluation in the p53+/- transgenic mouse model.
R E Stoll1, H E Holden, C H Barthel
1Department of Toxicology and Safety Assessment, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877, USA. rstoll@rdg.boehringer-ingelheim.com
Toxicologic Pathology
|October 21, 1999
Summary
Oxymetholone did not cause cancer in p53 heterozygous mice, despite causing physical changes. This suggests the p53 mouse model may not detect nongenotoxic carcinogens effectively.
Area of Science:
- Toxicology
- Carcinogenesis
- Transgenic Models
Background:
- Oxymetholone, a synthetic androgen, is a suspected nongenotoxic carcinogen.
- Its toxicological profile is being investigated using short-term transgenic mouse models.
- This study evaluates oxymetholone's carcinogenicity in p53 heterozygous mice before National Toxicology Program (NTP) results are disclosed.
Discussion:
- Oxymetholone administration induced significant body weight gain, clitoral enlargement in females, and altered organ weights (kidney, liver, testis).
- No neoplastic lesions were observed in oxymetholone-treated mice.
- Positive control p-cresidine induced bladder neoplasms, validating the model's sensitivity to genotoxic carcinogens.
Key Insights:
- Oxymetholone is devoid of mutagenic activity.
- The p53 heterozygous mouse model did not detect neoplastic lesions from oxymetholone exposure.
- The p53 mouse model appears selective for genotoxic carcinogens.
Outlook:
- Further research is needed to understand the limitations of the p53 mouse model for nongenotoxic carcinogens.
- Investigating alternative transgenic models may be necessary for comprehensive carcinogenicity assessment.
- This study contributes to the validation of short-term assays for carcinogen detection.