Journal Article

Study of post-natal effect of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. III. Inhibitory action of indomethacin, voltaren, theophylline and ɛ-aminocaproic acid

Valerij A. Alexandrov, Vladimir G. Bespalov, Algerd S. Petrov, Dmitrij N. Troyan and Margeris Yu. Lidaks

in Carcinogenesis

Volume 17, issue 9, pages 1935-1939
Published in print September 1996 | ISSN: 0143-3334
Published online September 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.9.1935
Study of post-natal effect of chemopreventive agents on
                    ethylnitrosourea-induced transplacental carcinogenesis in rats. III. Inhibitory
                    action of indomethacin, voltaren, theophylline and ɛ-aminocaproic
                    acid

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The influence of the arachidonic acid metabolism inhibitors, indomethacin and voltaren; an inhibitor of phosphodiester-ase activity, theophylline and the protease inhibitor ɛ-aminocaproic acid (EACA) on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure 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 were killed at 12 months. In the ENU-only control groups, 100% of the offspring developed tumors of brain, spinal cord, peripheral nervous system or kidneys, with a total average number of 3.1 tumors per rat The most marked inhibitory effect was exerted by theophylline, which significantly decreased the incidence and multiplicity of total tumors, and at all main sites selectively (brain, spinal cord, peripheral nerves and kidneys). It also prolonged average survival time of the offspring. Indomethacin and voltaren significantly decreased total tumor incidence and multiplicity, and brain tumor incidence and multiplicity. Indomethacin also decreased kidney tumor multiplicity and voltaren diminished spinal cord tumor multiplicity. EACA decreased multiplicities of total, brain, peripheral nerve and kidney tumors, and diminished the incidence of brain tumors. These chemopreventive agents decreased tumor incidences 20–33% and tumor multiplicities 1.4–2.7 times, compared with the ENU-only controls.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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