Acute response of the mouse bladder to derivatives of 4-ethylsulphonylnaphthalene-1-sulphonamide and bladder carcinogens measured by the uptake of (125 I)5-iodo-2 -deoxyuridine

The structural features of 4-ethylsulphonylnaphthalene-1-sulphonamide (ENS) responsible for the induction of DNA synthesis in the mouse bladder have been investigated using a method in which DNA synthesis is measured by the uptake of a thymidine analogue, [¹²⁵I]5-iodo-2′-deoxyuridine (IUdR). The ability to stimulate DNA synthesis was unaffected by the nature of the alkyl group in 4-alkylsulphonylnaphthalene-1-sulphonamide. The sulphonamide group appeared to be essential to the activity of the molecule because naphthalene-1,4-disulphonamide was active whereas 1,4-diethylsulphonylnaphthalene was not. Maximum activity was found when the sulphonamide group was attached to an aromatic system (benzene or naphthalene) containing an alkylsulphonyl or a sulphonamide group. Bladder carcinogens other than ENS failed to stimulate the uptake of [¹²⁵I]IUdR sufficiently to produce statistically significant results. The reasons for the large variation in response between individual mice are discussed, as are the implications of the structure activity relationships to the mode of action of ENS.