Experimental model for investigating bladder carcinogen metabolism using the isolated rat urinary bladder.
The capacity of the isolated rat urinary bladder to metabolize chemical carcinogens was studied. Under our experimental conditions, the bladder carcinogen N-nitrosobutyl-(4-hydroxybutyl)amine (NBHBA) was oxidized to N-nitrosobutyl(3-carboxypropyl)amine (NBCPA). A time-dependent increase in the amount of NBCPA formed and a simultaneous disappearance of NBHBA indicated that the bladder can metabolize NBHBA to the metabolite considered to be responsible for tumour induction in the urinary bladder of laboratory animals. After 15, 30, 60 and 120 min, the percentages of NBCPA formed were 10%, 21%, 35% and 61%, respectively, and 59%, 49%, 36% and 25% of NBHBA remained unchanged. When N-nitrosodi-n-butylamine (NDBA) was introduced into the isolated urinary bladder and incubated for 120 min, its oxidized metabolites NBHBA and NBCPA were formed, in amounts of 0.13% and 0.06% of the substrate added.
Airoldi
L
L
Laboratory of Environmental Pharmacology and Toxicology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bonfanti
M
M
Magagnotti
C
C
Fanelli
R
R
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics*; D009602:Nitrosamines / Q000493:pharmacokinetics; D051381:Rats; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D002273:Carcinogens; D009602:Nitrosamines; C006853:butyl(3-carboxypropyl)nitrosamine