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Abstracts on the effect of light and dark exposure on cancer development:
Int J Cancer 2004;111(4): 475-9 Effect of exposure to light-at-night on life span and spontaneous carcinogenesis in female CBA mice. VN Anisimov, DA Baturin, IG Popovich, MA Zabezhinski, KG Manton, AV Semenchenko, and AI Yashin
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, St. Petersburg , Russia . aging@mail.ru
The effect of constant illumination on the development of spontaneous tumors in female CBA mice was investigated. Fifty female CBA mice starting from the age of 2 months were kept under standard light/dark regimen (12 hr light:12 hr dark; LD) and 50 CBA mice of similar age were kept under constant illumination (24 hr a day, 2,500 Lux, LL). Exposure to the LL regimen decreased food consumption but did not influence body weight, significantly accelerated age-related disturbances in estrous function, and was followed by a significant increase in spontaneous tumor incidence in female CBA mice. Tumor incidence as well as the number of total or malignant tumors was significantly increased in the LL group compared to the LD group (p < 0.001). The incidence of lung adenocarcinomas, leukemias and hepatocarcinomas was 7/50; 6/50 and 4/50 in the LL group and 1/50; 0/50 and 0/50 in the LD group. Mice from the LL groups had shorter life spans then those from the LD group. The data demonstrate, for the first time, that exposure to constant illumination was followed by increases in the incidence of spontaneous lung carcinoma, leukemias and hepatocarcinoma in female CBA mice.
Publication Types: Journal article PMID: 15239122 -----------------------------------------------------------------------------------
Neuro Endocrinol Lett. 2001 Dec;22(6):441-7. The effect of light regimen and melatonin on the development of spontaneous mammary tumors in HER-2/neu transgenic mice is related to a downregulation of HER-2/neu gene expression.
Baturin DA, Alimova IN, Anisimov VN, Popovich IG, Zabezhinski MA, Provinciali M, Mancini R, Franceschi C.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St.Petersburg 197758, Russia.
OBJECTIVES AND DESIGN: The effect and the mechanism of light regimen and melatonin on the development of mammary tumors in HER2/neu transgenic mice were investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen (LD) or constant light illumination (LL) and a part of each group was given melatonin (20 mg/l) during the night time. RESULTS: The exposure to LL failed to change the incidence of spontaneous mammary adenocarcinoma development, the size of mammary tumors, as well as the incidence and size of lung metastases. However, the number of tumors per mouse was significantly increased in the LL group as compared to the LD group. The number of mice bearing 4 and more tumors was higher in the LL group than in the LD group, whereas the number of mice bearing 1 to 3 tumors was lower in the LL group in comparison with the LD group. Melatonin decreased the incidence and size of mammary adenocarcinomas, and the incidence of lung metastases in the LD group but not in the LL group. The mean number of tumors per mouse was not changed by melatonin treatment in both light regimens. The number of mice bearing 4 and more tumors was reduced by melatonin more significantly in the LL group than in LD group. Melatonin treatment resulted in a 2.5-fold reduction in the expression of HER-2/neu mRNA in mammary tumors from HER-2 /neu transgenic mice. CONCLUSION: The data demonstrate the influence of the LD light regiment and melatonin treatment in the development of spontaneous mammary tumors in HER-2/neu mice suggesting a melatonin-dependent modulation of HER-2/neu gene expression in mammary adenocarcinoma.
PMID: 11781542 [PubMed - indexed for MEDLINE] -----------------------------------------------------------------------
Exp Toxicol Pathol. 2000 Jun;52(3):221-5. Incidence and spectrum of spontaneous neoplasms in male and female CBA/J mice.
Tillmann T, Kamino K, Mohr U.
Institute of Experimental Pathology, Hannover Medical School, Germany. Tillmann@ita.fhg.de
Although CBA mice are occasionally used in biomedical research, little is known about their life-data and diseases ("background pathology"). Therefore, it was the aim of this study to determine the life expectancy, spectrum and incidence of spontaneous neoplasms of the inbred CBA/J mouse strain. A total of 631 untreated mice (293 females; 338 males) were kept from birth to death under standard laboratory conditions. A complete histological examination was performed on all organs/tissues. In female CBA mice, the average lifespan was 94 weeks, while the mean age in males was 85 weeks. Neoplastic lesions were observed in 70% (238/338) of the males and 51% (150/293) of the female CBA/J mice. Tumours of the liver, lung and haematopoietic tissue were common in males, while tumours of the lung, ovary and haematopoietic tissue were the most frequent neoplasms in female CBA/J mice.
PMID: 10930122 [PubMed - indexed for MEDLINE]
-------------------------------------------------------------------------------- Int J Cancer. 2003 Jan 20;103(3):300-5 The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER-2/neu transgenic mice.
Anisimov VN, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Manton KG, Semenchenko AV, Yashin AI.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia. aging@mail.ru
The effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given melatonin with tap water (20 mg/l) during the night time 5 times monthly (interrupted treatments) or constantly to natural death. Intact mice served as controls. Treatment with melatonin slowed down age-related disturbances in estrous function most in the group exposed to interrupted treatment with the hormone. Constant treatment with melatonin decreased incidence and size of mammary adenocarcinomas, and incidence of lung metastases, compared to controls. The number of mice bearing 4 and more tumors was reduced in the group with constant melatonin treatment. Interrupted treatment with melatonin promote mammary carcinogenesis in HER-2/neu transgenic mice. The data demonstrate the regimen-dependent inhibitory effect of melatonin on the development of spontaneous mammary tumors in HER-2/neu mice but not on overall survival with implication about the likely cause of the effect. Polycystic kidney disease is common in this transgenic line. Adverse effect of melatonin on the life span in our study may be unique to the transgenic model used and may not be relevant to the suppressive effect of melatonin in delay of mammary cancer. Copyright 2002 Wiley-Liss, Inc.
PMID: 12471612 [PubMed - indexed for MEDLINE]
-------------------------------------------------------------------------------- Neuro Endocrinol Lett. 2002 Jul;23 Suppl 2:28-36. The light-dark regimen and cancer development.
Anisimov VN.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758, Russia. aging@mail.ru
The role of the modulation of the pineal gland function in development of cancer is discussed in the review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen.
Publication Types: Review Review Literature
PMID: 12163845 [PubMed - indexed for MEDLINE] --------------------------------------------------------
J Gerontol A Biol Sci Med Sci. 2001 Jul;56(7):B311-23. Melatonin increases both life span and tumor incidence in female CBA mice.
Anisimov VN, Zavarzina NY, Zabezhinski MA, Popovich IG, Zimina OA, Shtylick AV, Arutjunyan AV, Oparina TI, Prokopenko VM, Mikhalski AI, Yashin AI.
N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia. aging@mail.ru
From the age of 6 months until their natural deaths, female CBA mice were given melatonin with their drinking water (20 mg/l) for 5 consecutive days every month. Intact mice served as controls. The results of this study show that the consumption of melatonin did not significantly influence food consumption, but it did increase the body weight of older mice; it did not influence physical strength or the presence of fatigue; it decreased locomotor activity and body temperature; it inhibited free radical processes in serum, brain, and liver; it slowed down the age-related switching-off of estrous function; and it increased life span. However, we also found that treatment with the used dose of melatonin increased spontaneous tumor incidence in mice. For this reason, we concluded that it would be premature to recommend melatonin as a geroprotector for long-term use.
PMID: 11445596 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------------
Vopr Onkol. 2000;46(3):311-9. [The effect of melatonin on the indices of biological age, on longevity and on the development of spontaneous tumors in mice]
[Article in Russian]
Anisimov VN, Zavarzina NIu, Zabezhinskii MA, Popovich IG, Anikin IV, Zimina OA, Solov'ev MV, Shtylik AV, Arutiunian AV, Oparina TI, Prokopenko VM, Khavinson VKh.
N. N. Petrov Research Institute of Oncology, Ministry of Health of the RF, St. Petersburg.
Fifty female CBA mice were given melatonin with drinking water (20 mg/l) for 5 consecutive days monthly, beginning from the age of 6 months, until natural death. Another 50 intact mice were used as controls. Melatonin failed to significantly influence body weight or food consumption. Age-related switching-off of estrus function was delayed, body temperature decreased. Somewhat decreased motor activity did not affect physical one or endurance. Increase in life span led to higher spontaneous tumor incidence. Another experiment using 20 animals of the same line showed melatonin to inhibit free-radical processes. A conclusion was drawn that caution should be exercised before melatonin is recommended for long-term administration as a geroprotector.
PMID: 10976278 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------
Cancer Lett. 2001 Feb 10;163(1):51-7. Effect of light/dark regimen on N-nitrosoethylurea-induced transplacental carcinogenesis in rats.
Beniashvili DS, Benjamin S, Baturin DA, Anisimov VN.
Department of Pathology, G. Wolfson Medical Center, Holon, Israel.
Pregnant females were randomly subdivided into three groups (24 rats per group) and kept at the 12:12 h light/dark regimen (group 1), at the constant light illumination (24 h a day, group 2) or at the continuous darkness (group 3). N-nitrosoethylurea (NEU) has been injected into the tail vein of all rats (80 mg/kg) on the 18-19th day of the pregnancy. After the delivery the lacting dams and their progeny during the lactation period (1 month after delivery) were kept also at the three different light/dark regimens. Then all offspring from each group was kept at the 12:12 h light/dark regimen, males and females separately, and were observed until natural death. The exposure to constant light significantly promoted the transplacental carcinogenesis whereas the exposure to constant darkness inhibited it. The incidence of total tumors, tumors of both a peripheral nervous system and kidney was 2.6; 2.5 and 8.5 times higher, and survival significantly shorter, correspondingly, in rats from the group 2 exposed to the constant light regimen as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). On the other hand, the exposure to the continuous darkness during the pregnancy and the lactation period significantly inhibited the transplacental carcinogenesis in the offspring of rats treated with NEU. The incidence of total tumors, tumors of a peripheral nervous system was by 2.4 and 2.7 times less, and survival longer, respectively, in exposed to the darkness rats from the group 3 as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). Thus, our data firstly have shown the modifying effect of light-dark regimen on the realization of the transplacental carcinogenesis induced by NEU in rats.
PMID: 11163108 [PubMed - indexed for MEDLINE] ------------------------------------------------------------------------------ Cancer Lett. 2001 Feb 10;163(1):51-7. Effect of light/dark regimen on N-nitrosoethylurea-induced transplacental carcinogenesis in rats.
Beniashvili DS, Benjamin S, Baturin DA, Anisimov VN.
Department of Pathology, G. Wolfson Medical Center, Holon, Israel.
Pregnant females were randomly subdivided into three groups (24 rats per group) and kept at the 12:12 h light/dark regimen (group 1), at the constant light illumination (24 h a day, group 2) or at the continuous darkness (group 3). N-nitrosoethylurea (NEU) has been injected into the tail vein of all rats (80 mg/kg) on the 18-19th day of the pregnancy. After the delivery the lacting dams and their progeny during the lactation period (1 month after delivery) were kept also at the three different light/dark regimens. Then all offspring from each group was kept at the 12:12 h light/dark regimen, males and females separately, and were observed until natural death. The exposure to constant light significantly promoted the transplacental carcinogenesis whereas the exposure to constant darkness inhibited it. The incidence of total tumors, tumors of both a peripheral nervous system and kidney was 2.6; 2.5 and 8.5 times higher, and survival significantly shorter, correspondingly, in rats from the group 2 exposed to the constant light regimen as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). On the other hand, the exposure to the continuous darkness during the pregnancy and the lactation period significantly inhibited the transplacental carcinogenesis in the offspring of rats treated with NEU. The incidence of total tumors, tumors of a peripheral nervous system was by 2.4 and 2.7 times less, and survival longer, respectively, in exposed to the darkness rats from the group 3 as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). Thus, our data firstly have shown the modifying effect of light-dark regimen on the realization of the transplacental carcinogenesis induced by NEU in rats.
PMID: 11163108 [PubMed - indexed for MEDLINE]
----------------------------------------------------------------------- Crit Rev Oncol Hematol. 2003 Jun;46(3):221-34 The role of pineal gland in breast cancer development.
Anisimov VN.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, 197758, St. Petersburg, Russia. aging@mail.ru
The role of the modulation of the pineal gland function in development of breast cancer is discussed in this review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits mammary carcinogenesis in pinealectomized rats, in animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen. Pineal peptide preparation Epithalamin and synthetic tetrapeptide Epitalon (Ala-Glu-Asp-Gly) are potent inhibitors of mammary carcinogenesis in rodents and might be useful in the prevention of breast cancer in women at risk.
PMID: 12791421 [PubMed - indexed for MEDLINE]
-------------------------------------------------------------------------------- Exp Gerontol. 2003 Apr;38(4):449-61. Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice.
Anisimov VN, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Rosenfeld SV, Manton KG, Semenchenko AV, Yashin AI.
N.N. Petrov Research Institute of Oncology, Pesochny-2, St.Petersburg 197758, Russian Federation. aging@mail.ru
From the age of 3 months until their natural death, female Swiss-derived SHR mice were given melatonin with their drinking water (2 or 20mg/l) for 5 consecutive days every month. Intact mice served as controls. There were 54 mice in each group. The results of this study show that the treatment of melatonin did not significantly influence food consumption, but its administration at lower doses did decrease the body weight of mice; it slowed down the age-related switching-off of estrous function; it did not influence the frequency of chromosome aberrations in bone marrow cells; it did not influence mean life span; and it increased life span of the last 10% of the survivors in comparison to controls. We also found that treatment with low dose melatonin (2mg/l) significantly decreased spontaneous tumor incidence (by 1,9-fold), mainly mammary carcinomas, in mice whereas higher doses (20mg/l) failed to influence tumor incidence as compared to controls. For this reason, we conclude that the effect of melatonin as a geroprotector is dose-dependent.
PMID: 12670632 [PubMed - indexed for MEDLINE]
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