The chemopreventive efficacy of
dehydroepiandrosterone (
DHEA) and
indomethacin (IM) alone or in combination was investigated in a rat multiorgan
carcinogenesis model. These two chemicals were selected as chemopreventive agents with different functions. Animals were sequentially given five
carcinogens with different organ target sites in the first 4-week initiation period. One week after its completion, the rats received 0.3%
DHEA in the diet, 20 ppm IM in the
drinking water, or 0.3%
DHEA + 20 ppm IM until experimental week 28.
DHEA enhanced hepatocarcinogenesis, but concurrent treatment with IM suppressed
tumor development as compared to the
DHEA group.
DHEA inhibited
tumor development in the thyroid, with a similar tendency observed for the small intestine. In addition, treatment with this
hormone decreased occurrences of preneoplasias in the urinary bladder and seminal vesicles. Treatment with IM clearly suppressed development of preneoplasias or
neoplasias in the lung and small and large intestines. In the urinary bladder, treatment with IM tended to decrease preneoplastic lesion development. Analysis of multiplicity of total
tumors of any category revealed comparable values for
DHEA and control groups, while the IM group showed a significant reduction. IM in combination with
DHEA caused suppression as compared to
DHEA alone. In a separate 8-week experiment,
DHEA or IM were administered for 4 weeks after prior
carcinogen application, and biochemical responses in the target organs were investigated.
DHEA increased
glucose-6-phosphate dehydrogenase levels in the liver but caused a decrease in the small intestine. In addition,
DHEA decreased serum T4 but not T3. IM decreased
prostaglandin E2 content in the small intestine. In conclusion, although
DHEA or IM exert significant chemopreventive effects in multiorgans with the exception of the
DHEA-treated liver case, treatment in combination did not result in amplification of their beneficial influence. Our results suggest the possible application of IM for
chemoprevention in high-risk individuals, but the question of effects of
DHEA in the liver must be answered before this
hormone can be considered for use in humans.