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Primary cardiac hemangiosarcomas induced by 1,3-butadiene in B6C3F1 hybrid mice
H A Solleveld1, R A Miller, D A Banas
1National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Insights
Chronic inhalation of 1,3-butadiene caused heart vascular lesions in mice. Females showed a dose-response relationship for hemangiosarcoma and endothelial hyperplasia, unlike males due to lower survival rates.
Area of Science:
- Toxicology
- Pathology
- Oncology
Background:
- 1,3-butadiene is a known industrial chemical.
- Proliferative vascular lesions in the heart are rare in mice.
- The cardiotoxicity of 1,3-butadiene requires further investigation.
Purpose of the Study:
- To investigate the effects of chronic 1,3-butadiene inhalation on the heart vasculature in mice.
- To characterize the histological and ultrastructural features of induced lesions.
- To determine the dose-response relationship and metastatic potential.
Main Methods:
- Mice were exposed to 1,3-butadiene via inhalation.
- Lesions were classified histologically as endothelial hyperplasia and hemangiosarcoma.
- Ultrastructural analysis was performed on hemangiosarcomas.
- Metastasis was assessed in other organs.
Main Results:
- Overall incidence of proliferative vascular lesions was 30% in males and 43% in females.
- Hemangiosarcoma incidence was 23% in males and 30% in females.
- A dose-response was observed in females, but not males, likely due to survival rates.
- Metastatic lesions were found in the liver, lung, and kidney.
Conclusions:
- 1,3-butadiene induces proliferative vascular lesions in the mouse heart.
- This study identifies 1,3-butadiene as a unique carcinogen targeting cardiac vasculature.
- Further research is needed to understand the mechanisms of 1,3-butadiene-induced cardiotoxicity.
Abstract:
Proliferative vascular lesions of the heart were found in mice exposed chronically to 1,3-butadiene by inhalation with an overall incidence of 30% in males and 43% in females. Based on histological criteria, the lesions were subclassified as endothelial hyperplasia with an incidence of 7% in males and 13% in females and hemangiosarcoma with an incidence of 23% and 30%, respectively. A dose-relationship for both lesions was observed in females, but not in males. The absence of a dose response in males was most likely due to the lower survival rate for high-dose animals (14%) when compared to the lower-dose animals (22%). Endothelial hyperplasia was characterized by widened vascular spaces lined by a single layer of plump endothelial cells. When cellular pleomorphism and piling up of endothelial nuclei were observed, the lesion was diagnosed as hemangiosarcoma. Ultrastructural examination of hemangiosarcomas revealed lumen formation, intercellular junctions and cytoplasmic filaments. Pinocytotic vesicles which are 1 of the characteristics of endothelial cells could not be identified with certainty. Weibel-Palade bodies were not detected in the neoplastic endothelium. Metastatic lesions were observed in liver, lung and kidney. To date, 1,3-butadiene is the only carcinogen reported that induces proliferative vascular lesions in the heart of mice.