Influence of various light regimes on some circadian rhythms of transplantable melanoma B16

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Abstract

BACKGROUND: Today it is known that disturbance of the lighting regime, expressed both by lengthening of the light period and its reduction, can not only affect the regulation of circadian rhythms of the organism, but also contributes to the initiation of neoplasm growth.

AIM: The aim of the study was to investigate circadian rhythmicity of melatonin level, some micromorphometric indices of tumor cells and expression of genes Bmal1, Clock and Per2 in them in mice with transplanted melanoma B16.

MATERIALS AND METHODS: The study was conducted on 75 mice with subcutaneously transplanted melanoma B16, divided into 3 groups: control group, in which animals were kept under fixed light regime (light/darkness 10/14 hours with light on at 8:00 and off at 18:00), group under dark deprivation conditions, with animals kept under constant light 24 hours a day and group, in which animals were kept in constant darkness. The duration of the experiment was 2 weeks.

RESULTS: It was shown that under conditions of fixed light there are reliable circadian rhythms for all studied parameters, except for the nuclear-cytoplasmic ratio, the circadian rhythms of which was not revealed in any group. Constant darkness leads to rearrangement of all identified rhythms, and constant light causes destruction of all circadian rhythms except the Clock expression rhythm.

CONCLUSIONS: This study shows that light disturbances, whether constant light or constant darkness, lead to significant changes in the structure of the studied circadian rhythms.

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About the authors

David A. Areshidze

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Author for correspondence.
Email: labcelpat@mail.ru
ORCID iD: 0000-0003-3006-6281
SPIN-code: 4348-6781

Cand. Sci. (Med.), Head of Laboratory of Cell Pathology

Russian Federation, 3 Tsuryupy St., Moscow, 117418

Maria A. Kozlova

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Email: ma.kozlova2021@outlook.com
ORCID iD: 0000-0001-6251-2560
SPIN-code: 5647-1372

Cand. Sci. (Biol.), Senior Research Associate of Laboratory of Cell Pathology

Russian Federation, 3 Tsuryupy St., Moscow, 117418

Denis V. Mishchenko

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry Russian Academy of Sciences

Email: mdv@icp.ac.ru
ORCID iD: 0000-0003-3779-3211
SPIN-code: 4213-3318

Cand. Sci. (Biol.), Leading Research Associate of Experimental Tumor Chemotherapy Group

Russian Federation, Chernogolovka

Valery P. Chernikov

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Email: 1200555@mail.ru
ORCID iD: 0000-0002-3253-6729
SPIN-code: 3125-7837

MD, Cand. Sci. (Med.), Leading Research Associate of Laboratory of Cell Pathology

Russian Federation, 3 Tsuryupy St., Moscow, 117418

Tatyana V. Bezuglova

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Email: bezuglovat@mail.ru
ORCID iD: 0000-0001-7792-1594
SPIN-code: 3943-4400

Cand. Sci. (Biol.), Deputy Director for Scientific Work

Russian Federation, 3 Tsuryupy St., Moscow, 117418

Maxim V. Mnikhovich

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Email: mnichmaxim@yandex.ru
ORCID iD: 0000-0001-7147-7912
SPIN-code: 6975-6677

MD, Cand. Sci. (Med.), Leading Research Associate of the Central Pathology Laboratory

Russian Federation, 3 Tsuryupy St., Moscow, 117418

Zarina V. Gioeva

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Email: gioeva_z@mail.ru
ORCID iD: 0000-0002-5456-8692
SPIN-code: 9210-9726

MD, Cand. Sci. (Med.), Head of the Central Pathology Laboratory

Russian Federation, 3 Tsuryupy St., Moscow, 117418

Uguljan Yu. Allayarova

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry Russian Academy of Sciences

Email: bezuglovat@mail.ru
ORCID iD: 0000-0002-8264-0997
SPIN-code: 4996-3473

Junior Research Associate of Experimental Tumor Chemotherapy Group

Russian Federation, Chernogolovka

Anna I. Anurkina

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry Russian Academy of Sciences

Email: anyaaai1925@gmail.com
ORCID iD: 0009-0003-0011-1114
SPIN-code: 9812-3412

Research Assistant of Laboratory of Cell Pathology

Russian Federation, Chernogolovka

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  63. Sugden D, Davidson K, Hough KA, et al. Melatonin, melatonin receptors and melanophores: a moving story. Pigment Cell Res. 2004;17(5):454–460. doi: 10.1111/j.1600-0749.2004.00185.x
  64. Vriend J, Reiter RJ. Melatonin feedback on clock genes: a theory involving the proteasome. J Pineal Res. 2015;58(1):1–11. doi: 10.1111/jpi.12189
  65. Rodríguez-Santana C, Florido J, Martínez-Ruiz L, et al. Role of melatonin in cancer: Effect on clock genes. Int J Mol Sci. 2023;24(3):1919. doi: 10.3390/ijms24031919

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Daily dynamics of melatonin content in the blood of mice. *** p ≤ 0,0005 in comparison with the indicators at 9:00; ### р ≤ 0,0005 in comparison with the indicators at the previous time point. Here and further: СС — I experimental group; TT — II experimental group; Control — control group

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3. Fig. 2. Results of cosinor analysis of the daily dynamics of melatonin content in the blood of mice

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4. Fig. 3. Daily dynamics of the studied micromorphometric parameters of B16 melanoma cells: a — nuclei area; b — cell area; c — nuclear-cytoplasmic ratio. * p ≤ 0,05, ** p ≤ 0,005, *** p ≤ 0,0005 in comparison with the indicators at 9:00; # p ≤ 0,05, ## р ≤ 0,005, ### р ≤ 0,0005 in comparison with the indicators at the previous time poin

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5. Fig. 4. Results of cosinor analysis of the daily dynamics of the area of the nucleus (a), cell (b) and nuclear-cytoplasmic ratio (c) of B16 melanoma cells

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6. Fig. 5. Daily dynamics of expression of the studied genes in B16 melanoma cells: a — Bmal1; b — Clock; c — Per2. * p ≤ 0,05, ** p ≤ 0,005, *** p ≤ 0,0005 in comparison with the indicators at 9:00; # p ≤ 0,05, ## р ≤ 0,005, ### р ≤ 0,0005 in comparison with the indicators at the previous time point

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7. Fig. 6. Results of cosinor analysis of the daily dynamics of expression of Bmal1 (a), Clock (b) and Per2 (c) in B16 mela- noma cells

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