Carcinogenecity of the N-acyl derivatives of N-hydroxy-trans-4-aminostilbene in CD rats

Tissue specificities of tumor induction by aromatic amines

“…Direct injection of suitable AA derivatives into the mammary gland at an appropriate time in the development of female rats leads to the development of mammary tumors. Such experiments have convincingly demonstrated that arylhydroxamic acids are the most effective AA-derived structures using this technique (10)(11)(12). One advantage of this technique is that neither tumor induction nor metabolism of the test compound is dependent on systemic effects.…”

“…For example, tumor induction results from direct exposure of susceptible tissues by synthetic N-oxidized derivatives, such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) in rats, but not by the parent amide. Thus circumventing the requirement for systemic metabolic N-oxidation, oral administration induces tumors of the forestomach (4), bladder tumors on instillation into the urinary bladder (5-7), and tumors on direct injection into the peritoneal cavity (8)(9)(10) or mammary gland (11)(12). These observations directly implicate a non-reactive N-oxidized compound in the transformation process within the target tissue by a putative metabolic activation event.…”