The influence of the
arachidonic acid metabolism inhibitors,
indomethacin and
voltaren; an inhibitor of
phosphodiesterase activity,
theophylline and the
protease inhibitor epsilonaminocaproic
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.