The foci of aberrant crypts and changes of microbiota of gut upon chemical mutagenesis and experimental hyperand hypothyroid status

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Abstract

In our paper we present data on the induction of nitrosomethylurea focuses of aberrant crypts on experimentally altered thyroid status in mice and concomitant changes in the intestinal microbiota. Since the foci of aberrant crypts are an obvious prerequisite for long-range malignancy in colorectal cancer, the induction of colorectal cancer induced by nitrosomethylurea is the most appropriate model for investigating mechanisms of carcinogenesis. Male BALB / c male mice which were treated with nitrosomethylurea (NMU) for 24 weeks when also combined with L-thyroxin or propylthiouracil were used in the study. The results indicate that the incidence of aberrant crypt foci (FAC) was significantly higher for a group of animals which were treated with both NMU and L-thyroxin 38.9 ± 3.6%. At the same time the incidence of FAC with hyperthyroid status only without exposure to NMU was also high at 12.9 ± 4.2%. It was shown that the hypothyroid status had a significant protective effect on the intestinal epithelium when exposed to HMN – 16.1 ± 2.5%. A significant quantitative decrease in Lactobacillus spp. of microbiome was detected in groups of mice exposed not only to NMU, but also in animals with experimentally induced hyperthyroid status only. Mechanisms that contribute to the occurrence of an increased frequency of FAC in the context of hyper- and hypothyroid status are discussed. It was concluded that an increased incidence of foci of aberrant crypts and a decrease in the quantity of the normal microbiota are associated with hyperthyroid status which modulated upon administration of methylnitrosourea.

About the authors

Sergei N. Proshin

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: psnjsn@rambler.ru

MD, PhD, Dr Med Sci, Professor, Head, Department of Pharmacology

Russian Federation, Saint Petersburg

Ruslan A. Kurbanov

St Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation

Email: ruslan_kra@mail.ru

Postgraduate Student, Department of Operative Surgery and Topographic Anatomy

Russian Federation, Saint Petersburg

Svyatoslav I. Loskutov

Limited Liability Company “Scientific production association “BioEcoTech”

Email: info@bioecotech.ru

General Director

Russian Federation, Saint Petersburg

Nikita N. Barsukov

North-Western State Medical University named after I.I. Mechnikov

Email: nikich.spn@gmail.com

Staff, Department of Pharmacology

Russian Federation, Saint Petersburg

Hajimurad O. Alibekov

North-Western State Medical University named after I.I. Mechnikov

Email: Knowledge-7780@mail.ru

Staff, Department of Pharmacology

Russian Federation, Saint Petersburg

Dmitrii A. Kachanov

North-Western State Medical University named after I.I. Mechnikov

Email: kachanov.dima@yandex.ru

Staff, Department of Pharmacology

Russian Federation, Saint Petersburg

Ruslan I. Glushakov

Military Medical Academy named after S.M. Kirov

Email: glushakovruslan@gmail.com

MD, PhD, Associate Professor, Department of Obstatrics and Gyneacology

Russian Federation, Saint Petersburg

Georgii O. Bagaturiya

St Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation

Email: geobag@mail.ru

MD, PhD, Dr Med Sci, Professor, Head, Department of Operative surgery and topographic anatomy

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Administration of methylnitrosourea by rectal catheter

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3. Fig. 2. Foci of aberrant crypts in rectal mucosa: а – normal rectal mucosa; b, c, d – foci of aberrant crypts indicated by arrows. Magnification ×400

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4. Fig. 3. Multiple foci of aberrant crypts in rectal mucosa of mice administered to methylnitrosourea and L-thyroxin. Magnification ×400

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5. Fig. 4. Total DNA. M – marker; 1 – group 1; 2 – group 2; 3 – group 3; 4 – group 4; 5 – group 5

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6. Fig. 5. PCR. M – marker; 1 – group 1; 2 – group 2; 3 – group 3; 4 – group 4; 5 – group 5

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Copyright (c) 2018 Proshin S.N., Kurbanov R.A., Loskutov S.I., Barsukov N.N., Alibekov H.O., Kachanov D.A., Glushakov R.I., Bagaturiya G.O.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
 


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