The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats

We investigated the effects of altered endogenous nighttime melatonin conce ntrations on mammary tumor production in an N-nitroso-N-methylurea (NMU)-in duced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting i n a decrease in nighttime serum melatonin concentrations. 2) to evaluate wh ether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppre ssed serum melatonin concentrations on the incidence and progression of NMU -induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-i nduced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light:dark cycle decreased the mag nitude of the nocturnal rise of serum melatonin concentrations in rats by a pproximately 65%. After 2 weeks of nightly intermittent light exposures. an average decrease of the peak nighttime serum melatonin concentrations of a pproximately 35% occurred. The amelioration continued and, at 10 weeks, pea k nighttime serum melatonin concentrations were still decreased, by approxi mately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multipl icity, and weight of NMU-induced mammary tumors were assessed. A group of p inealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were mod erately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 N MU controls, 28/40 NMU + light, 31/40 NMU + Pr). multiplicity (2.18 tumors/ tumor-bearing NMU control. 1.89 NMU + light, 2.39 NMU + Pr). or average tum or weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Pr). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, an imals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additiona lly, rats that had been pinealectomized at 4 weeks of age had serum melaton in concentrations that were markedly higher than the expected baseline conc entrations for pinealectomized rats (<15 pg/ml), suggesting the reestablish ment of a melatonin cycle. This finding was unexpected and suggests that me latonin can be produced by an organ or tissue other than the pineal gland.