Effect of the mammary carcinogen 7,12-dimethylbenz[a]anthracene on pineal melatonin biosynthesis, secretion and peripheral metabolism.

The aim of this study was to establish whether the nocturnal peak concentrations of circulating melatonin are affected by a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats as used for mammary tumor induction. Prior to this, the circadian rhythms of melatonin (N-acetyl-5-methoxytryptamine) and 6-sulfatoxymelatonin, the main metabolic product of melatonin, were determined in female Sprague-Dawley rats. The cosinor analysis revealed significant circadian rhythms with very similar acrophases around 1.00 a.m. for both substances. To enable explanations for possible changes in plasma melatonin after DMBA treatment, the biosynthesis in the pineal and the major metabolic product in the liver, 6-sulfatoxymelatonin, were measured 2 and 7 days after DMBA. Plasma melatonin was depressed by 31-37% (p less than 0.05) 2 and 7 days after DMBA but the pineal melatonin content remained unchanged. 2 days after DMBA, pineal serotonin and N-acetylserotonin showed a transient elevation of 35% (p less than 0.025) and 25% (p less than 0.05), respectively. The plasma concentrations of 6-sulfatoxymelatonin were the same in DMBA- and vehicle-treated animals. An elevation of the 6-sulfatoxymelatonin/melatonin ratio indicated a relative increase in the metabolism of melatonin due to DMBA. The absence of an absolute increase in 6-sulfatoxymelatonin after DMBA could be caused by an additional shift within the spectrum of different metabolic products of melatonin due to the carcinogen. Possible mechanisms are discussed.