Melatonin
Retards the Growth of Diethylstilbestrol-Induced Renal Tumors
in Male Syrian Hamsters by Bryant Benson
Abstract:
Chronic
diethylstilbestrol (DES) treatment of male Syrian hamsters results
in renal carcinoma. Whereas early neoplastic changes occur in
the first three to six months of DES treatment, the appearance
of frank tumors and metastases appear only after nine or ten
months. Our previous work has shown that short photoperiod exposure
retards the growth and metastatic spread of DES-induced renal
tumors in hamsters. The mechanisms involved in suppression of
tumor growth by light deprivation were not determined in these
studies, but increased melatonin (MEL) secretion may have played
a role. This hypothesis was tested in the present experiment.
Young adult, male Syrian hamsters (Lak:LVG) were maintained
in long photoperiod (14L:10D). Four groups of animals were established:
one group, designated DES, received SC 15 mm Silastic capsules
containing 5.0 mg of DES; a second group (DES + MEL) received
DES-filled capsules and MEL (0.5 µg/g body wt.) in their drinking
water. A control group was given empty Silastic capsules (CON)
and another group of controls empty capsules plus MEL (CON +
MEL). All capsules were replaced at four month intervals. Subgroups
of 12 hamsters from each of the four groups were killed at 3,
6 and 9 months. As expected, DES treatment effected an increase
in renal weight, total kidney protein and DNA at 3, 6 and 9
months. The increase in these parameters at 3 and 6 months reflected
the observed concomitant interstitial hyperplasia indicative
of early neoplastic changes. MEL was without significant effects
on body weight, kidney weight, protein and total DNA in the
CON + MEL animals. On the other hand, MEL treatment of hamsters
that received DES significantly attenuated the effects of DES
on kidney weight, kidney protein and total kidney DNA. Tumors
were not observed in DES treated until 9 months of treatment,
at which time abdominal metastases were also observed. Only
two of the 12 hamsters treated with DES + MEL and killed at
9 months showed small tumors on the surface of their kidneys.
No indications of metastases were noted in any of the hamsters
that received DES + MEL. These results suggest that MEL treatment
attenuates the growth of the DES-induced renal adenocarcinoma
in male hamsters but whether the effect is via a protective
effects on the postulated direct effect of DES on renal cells
or results from alterations in neuroendocrine and/or other mechanisms
remains to be investigated.
