This comprehensive study examines the influence of oral melatonin on the initiation and promotion phases of DMBA-induced mammary tumorigenesis in intact and pinealectomized female Holtzman rats reared in short (light:dark schedule L:D 10:14) and long (L:D 24:0) photoperiods. Melatonin administration in the initiation phase significantly suppressed tumor incidence only in intact animals reared in both photoperiods, indicating that the presence of the pineal was obligatory. On the other hand, during the promotion phase, irrespective of the presence or absence of the pineal, the tumor-suppressive effect of exogenous melatonin was pronounced.
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