Biotransformation of aromatic amines to DNA-damaging products by urinary bladder organ cultures.

Abstract

Urinary bladder is a target tissue for aromatic amine carcinogens. The intrinsic capacity of this tissue to form DNA-damaging products was investigated in explant cultures of bladder isolated from New Zealand white rabbits. DNA repair, measured by autoradiography, was used as the indicator of DNA damage. DNA repair was induced by 2-aminofluorene (2-AF) and its acetylated derivatives 2-acetyl-aminofluorene and N-hydroxy-2-acetylaminofluorene. A positive response was observed with benzidine (BZD), but no repair was seen in cultures exposed to monoacetyl BZD or diacetyl BZD. These results indicate that rabbit urinary bladder has the ability to biotransform aromatic amines to DNA-damaging products and has the capacity to repair damaged DNA. Unlike liver, where activation of BZD seems to require N-acetylation, acetylated BZD in the bladder appeared to be a detoxification product. The lack of damage by acetylated BZD is consistent with activation of BZD in bladder by prostaglandin synthetase-mediated pathways.