title: On the long-term toxic risk of dinaline.
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.
authors.affiliation: Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
authors.forename: M R
authors.initials: MR
authors.lastname: Berger
authors.forename: D
authors.initials: D
authors.lastname: Schmähl
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D010655:Phenylenediamines; C045838:dinaline