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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
On the long-term toxic risk of dinaline
1Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Abstract:
The long-term toxic risk of the cytostatic agent dinaline (4-amino-N-(2'-aminophenyl)-benzamide) was assessed in a rat bioassay. Regular administration of 9, 3 and 1 mg/kg for 106 weeks was associated with significantly increased survival of female rats receiving the median and low doses. Dinaline significantly reduced the occurrence of malignant tumors in male rats and prolonged the manifestation time of malignancies in female rats. Unlike malignant tumors, benign neoplasms were increased in male rats and were not significantly different from controls in female rats. Analysis of organ distribution of neoplastic lesions revealed a dose-dependently decreased tumor incidence in the hematopoietic and lymphatic tissue, the mammary gland (females only) and the pituitary gland and a not dose dependently reduced incidence of liver tumors. This contrasted with dose dependently increased tumor incidences in the adrenal gland, the gonads and the vagina. Considering these findings, dinaline has to be assessed as a modulator of carcinogenesis in rats. The observed decreased and increased tumor incidences suggest a hormone-related mechanism of action.
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