Background: Shift work has recently been identified as a breast cancer risk factor, where meta-analysis has indicated an approximately 50% increased risk among long-term shift workers. However, additional studies with more comprehensive methods of shift work exposure assessment are needed to capture the diversity of shift patterns. The hypothesized mechanism for this relationship involves chronodisruption (altered circadian rhythms), where increased exposure to light at night during night shifts may decrease production of the cancer-protective hormone melatonin. Further, coordination of circadian rhythms, including melatonin production, is governed by the interactions of a set of central clock genes. Recent studies have suggested that variants in clock genes are associated with cancer risk at multiple sites, including breast cancer, although few studies have considered potential interactions with shift work. Methods: This thesis examined relationships of both shift work and clock gene polymorphisms (and their interactions) with breast cancer risk in a case-control study of 1,142 cases and 1,178 controls. The association between light exposure and melatonin production was also investigated in a longitudinal biomarker study conducted among 123 nurses working a two-day, two-night rotating shift pattern. Results: In the case-control study, an association between breast cancer and ≥30 years of shift work (OR = 2.20, 95%CI = 1.13 – 4.28) was detected, although no relationship with short (0 – 14 years) or medium (15 – 29 years) term shift work was observed. As well, variants in 14 clock-related genes were not associated with breast cancer and there were no apparent interactions with shift work history. In the biomarker study, both peak melatonin levels and daily change in melatonin levels were similar when nurses were working their day and night shifts. Further, on the night shift, a slight inverse relationship between light and change in melatonin was observed (p = 0.04). Conclusions: Taken together, these results contribute to the understanding of both the association between shift work and breast cancer, and the biologic mechanisms underlying this relationship. Since shift work is required for many occupations, understanding the mechanisms through which it impacts breast cancer is important to the development of healthy workplace policy. / Thesis (Ph.D, Community Health & Epidemiology) -- Queen's University, 2012-09-26 20:59:40.209

Melatonin is a hormone secreted by the pineal gland, which is known to modulate biological rhythms in mammals. This study investigated the effect of food access schedule and dietary composition on serum melatonin and pineal NAT activity in adult male Wistar rats. These rats were maintained on a 12:12 h light:dark schedule with lights on at 0800h. The rats were randomly assigned to two dietary groups. A group was simultaneously fed a protein-rich and carbohydrate-rich granulated diet and the other group fed granulated rat chow. Each dietary group was further divided based on dietary feeding schedules. Animals were fed between 0800--1600 h or fed ad libitum. The study revealed that protein intake of rats fed the dietary choice was lower with the restricted access than in the free access. In rats fed dietary choice, the nocturnal melatonin levels and pineal NAT activity were significantly lower under the restricted access feeding when compared to the ad libitum feeding schedule. This was not observed in rats fed single chow diet. In conclusion our data demonstrate that food composition does affect the nocturnal synthesis of melatonin as well as the activity of the enzyme NAT. This could be via dietary intake of tryptophan, which is a precursor melatonin synthesis in the pineal gland.

Photoperiod is an important signal involved in the timing and co-ordination of many processes such as growth and reproduction in salmonids. Both growth and reproduction appear to be controlled by endogenous rhythms, which under natural conditions, is entrained by the seasonal changes in daylength, that is accurately reflected by the diel pattern of melatonin. This thesis investigates the influence of photoperiod on growth and reproduction in rainbow trout (Oncorhynchus mykiss), and examines the effect on plasma insulin-like growth factor-I (IGF-I). These studies aim to further our scientific understanding of the endocrine mechanisms controlling growth and reproduction and transfer this knowledge to commercial trout farming practices. Studies at fry (<5g) and fingerling (>25g) stages investigated the effect of exposure to constant long-days (LD18:6) and constant light (LL) on growth performance. In all experiments, there was a significant growth enhancing effect following exposure to extended light regimes relative to those under ambient or constant short-day photoperiods. Growth enhancement appeared to be caused through direct photo-stimulation or a phaseshift in an underlying endogenous rhythm dependent on the timing of photoperiod application. Measurement of plasma IGF-I accurately reflected growth rate during juvenile development. Furthermore, a clear autumnal increase in IGF-I was observed that was apparently up-regulated by long-day photoperiods. Additionally, it was shown that melatonin implants significantly reduced growth rate below that of unimplanted controls irrespective of photoperiod, but did not reduce circulating IGF-I levels suggesting that elevated melatonin levels masked the perception of daylength but did not act directly on the somatotropic axis to control growth. As size or one of its correlates (growth rate, energy balance or nutritional status) is regarded as an important determinant of the ability to undergo puberty, the interaction of natural (SNP) and advancing (ADV: long-short day) photoperiods with growth, IGF-I and reproduction was investigated in virgin female broodstock. Under SNP 63% of the population attained maturity while only 29% spawned in the ADV regime. Under SNP both size and growth rate in late spring/early summer appeared to determine whether an individual may initiate maturation. Conversely, under ADV, condition factor appeared to be a better predictor. A complete seasonal relationship between plasma IGF-I, daylength and temperature was demonstrated for the first time in rainbow trout under natural conditions, and provides direct evidence for the relationship between maturation and IGF-I. IGF-I levels showed a negative correlation with testosterone as fish initiated maturation. Furthermore, IGF-I levels accurately reflected growth rate prior to the initiation of vitellogenesis, suggesting that IGF-I may provide an endocrine signal between the somatotropic and reproductive axes that nutritional status, growth rate and/or size is sufficient to initiate maturation. In addition, maturing individuals under both photoperiods typically expressed higher circulating IGF-I levels than those that remained immature and may reflect a greater opportunity for IGF-I to act on the pituitary to stimulate gonadotropin production. In this sense, the observation of elevated levels for 3 months under SNP compared to only 1 month under ADV may reflect a reduction in the window of opportunity to initiate maturation under advancing photoperiods and hence explain the reduction in fish spawning. Finally, using a commercially available ELISA kit provided evidence of a possible detection method for measurement of a leptin-like peptide as absolute levels differed significantly between mature and immature fish. This provides preliminary evidence for a possible involvement of a leptin-like peptide in rainbow trout reproduction and energy homeostasis. Given the above evidence of a growth enhancing effect of photoperiod in covered systems, the transfer of constant light (LL) regimes to uncovered commercial trout farming practices was also examined. The application of LL regimes during either fry grow-out in tanks using floating lights or ongrowing to harvest size during winter in cages using submersible lights was investigated. In all trials conducted, the exposure to LL in autumn significantly enhanced winter growth rate and feeding efficiency by up to 30% and 25% respectively relative to those maintained under ambient light. Furthermore, the effect of light intensity was clearly shown to be an important requirement in successfully applying photoperiod regimes onto the ambient photoperiod in order to enhance commercial production in "uncovered systems". These studies clearly indicate the importance of photoperiod in influencing growth and reproduction in rainbow trout. Furthermore, the use of plasma IGF-I as an indicator of growth provides a practical tool for studying growth-photoperiod-reproduction interactions in this species. However, further studies are necessary to further our understanding of the endocrine pathways governing physiological mechanisms, especially growth and reproduction. Overall, this work has provided important information to improve both scientific understanding and commercial development although it is clear that substantial research is still required.

MOLECULAR INVESTIGATION OF THE EFFECTS OF ANTIOXIDANTS ON RAT BRAIN TISSUES

Bibliography: leaves 162-197. / vii, 216 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / To determine the effects of melatonin on sleepiness and body temperature under conditions that better approximated the endogenous melatonin profile. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1998?

Thesis (M. Sc.)--University of Adelaide, 1988. / Includes bibliographical references (leaves 131-150).

München, Techn. University, Diss., 2007.

Diss. (sammanfattning) Umeå : Univ., 2008. / Härtill 5 uppsatser.

Techn. University, Diss., 2005--Darmstadt.

Tez (Yüksek Lisans) - Süleyman Demirel Üniversitesi, Sağlık Bilimleri Enstitüsü, Biyokimya ve Klinik Biyokimya Anabilim Dalı, 2003. / Bibliyografya var.