STUDY OF POSTNATAL EFFECT OF CHEMOPREVENTIVE AGENTS ON ETHYLNITROSOUREA-INDUCED TRANSPLACENTAL CARCINOGENESIS IN RATS .3. INHIBITORY-ACTIONOF INDOMETHACIN, VOLTAREN, THEOPHYLLINE AND EPSILON-AMINOCAPROIC ACID

The influence of the arachidonic acid metabolism inhibitors, indometha cin and voltaren; an inhibitor of phosphodiesterase activity, theophyl line and the protease inhibitor epsilon-aminocaproic acid (EACA) on N- ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was st udied in rats. ENU was given to pregnant rats as a single i.v. exposur e at a dose of 75 mg/kg body weight on the 21st day after conception, Indomethacin and voltaren (20 p.p.m. in drinking water), theophylline (0.01% in diet) and EACA (1000 p.p.m. in drinking water) were given to the offspring throughout their post-natal life until all survivors we re killed at 12 months, In the ENU-only control groups, 100% of the of fspring developed tumors of brain, spinal cord, peripheral nervous sys tem or kidneys, with a total average number of 3.1 tumors per rat, The most marked inhibitory effect was exerted by theophylline, which sign ificantly decreased the incidence and multiplicity of total tumors, an d at all main sites selectively (brain, spinal cord, peripheral nerves and kidneys), It also prolonged average survival time of the offsprin g, Indomethacin and voltaren significantly decreased total tumor incid ence and multiplicity, and brain tumor incidence and multiplicity, Ind omethacin also decreased kidney tumor multiplicity and voltaren dimini shed spinal cord tumor multiplicity, EACA decreased multiplicities of total, brain, peripheral nerve and kidney tumors, and diminished the i ncidence of brain tumors, These chemopreventive agents decreased tumor incidences 20-33% and tumor multiplicities 1.4-2.7 times, compared wi th the ENU-only controls.