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

By Charlene A. Mcqueen and Barbara M. Vvay


Urinary bladder is a target tissue for aromatic amine car-cinogens. 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 in-dicator of DNA damage. DNA repair was induced by 2-aminofluorene (2-AF) and its acetylated derivatives 2-acetyl-aminofluorene and iV-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 blad-der 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 iV-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 prosta-glandin synthetase-mediated pathways

Year: 2016
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