The effect of NBS1 heterozygous inactivating mutation in a model of 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in mice
- Authors: Yurova M.N.1, Golubev A.G.1, Fedoros E.I.1, Tumanyan I.A.1, Von Y.D.1, Semenov A.L.1, Otradnova E.A.1, Imyanitov E.N.1
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Affiliations:
- N.N. Petrov National Medical Research Centre of Oncology
- Issue: Vol 28, No 1 (2023)
- Pages: 27-36
- Section: Original Study Articles
- URL: https://journals.rcsi.science/1028-9984/article/view/217181
- DOI: https://doi.org/10.17816/onco516564
- ID: 217181
Cite item
Abstract
BACKGROUND: The creation of new experimental models carrying various heterozygous inactivating mutations in DNA repair genes and their carcinogenesis studies could expand our understanding of the spectrum of possible neoplasms that patients with such mutations are at risk of developing.
AIM: The study of the effect of NBS1 inactivating heterozygous mutation (с.1971insT, p.Arg658Stop) in a model of 7,12-dimethylbenz[a]anthracene (DMBA) induced carcinogenesis in mice.
MATERIALS AND METHODS: Carcinogenesis was induced in 2-month-old female mice with and without NBS1 heterozygous mutation by intragastric administration of 7,12-DMBA (dose of 50 mg/kg once a week, for 8 weeks) on a high-fat diet. Lifetime observation was conducted, and parameters of lifespan and carcinogenesis were evaluated.
RESULTS: NBS1 inactivating heterozygous mutation had no significant effect on the incidence of tumor pathology induced by 7,12-DMBA, but somewhat accelerated the rate of tumor development and, consequently, the death of animals. The presence of the mutation increased the sensitivity to carcinogen toxic effect, which was expressed in a statistically significant increase in death rate (by 35%) in the early stages of the study. The mean lifespan in female NBS1 mutant mice was reduced by 14% compared to mutation-free animals.
CONCLUSION: Carrying NBS1 inactivating heterozygous mutation (с.1971insT, p.Arg658Stop) worsens the prognosis of survival in the model of chemically induced 7,12-DMBA carcinogenesis in mice.
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##article.viewOnOriginalSite##About the authors
Maria N. Yurova
N.N. Petrov National Medical Research Centre of Oncology
Author for correspondence.
Email: yumarni@gmail.com
ORCID iD: 0000-0003-3589-5871
SPIN-code: 3497-5175
Cand. Sci. (Bio.)
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint PetersburgAlexey G. Golubev
N.N. Petrov National Medical Research Centre of Oncology
Email: lxglbv@rambler.ru
ORCID iD: 0000-0002-2129-6205
SPIN-code: 2871-0779
Cand. Sci. (Bio.)
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint PetersburgElena I. Fedoros
N.N. Petrov National Medical Research Centre of Oncology
Email: elenafedoros@gmail.com
ORCID iD: 0000-0002-2426-9843
SPIN-code: 3302-1384
Cand. Sci. (Bio.)
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint PetersburgIrina A. Tumanyan
N.N. Petrov National Medical Research Centre of Oncology
Email: itumanyan@mail.ru
ORCID iD: 0000-0002-8926-1519
SPIN-code: 1165-4685
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint Petersburg
Yulia D. Von
N.N. Petrov National Medical Research Centre of Oncology
Email: takeo_yuki@mail.ru
ORCID iD: 0000-0002-5161-5940
SPIN-code: 8621-1112
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint Petersburg
Alexander L. Semenov
N.N. Petrov National Medical Research Centre of Oncology
Email: genesem7@gmail.com
ORCID iD: 0000-0002-5190-0629
SPIN-code: 4301-8679
MD, Cand. Sci. (Med.)
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint PetersburgEkaterina A. Otradnova
N.N. Petrov National Medical Research Centre of Oncology
Email: katya.otradnova@mail.ru
ORCID iD: 0009-0003-0158-1820
SPIN-code: 9861-0730
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint Petersburg
Evgeny N. Imyanitov
N.N. Petrov National Medical Research Centre of Oncology
Email: evgeny@imyanitov.spb.ru
ORCID iD: 0000-0003-4529-7891
SPIN-code: 1909-7323
MD, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences
Russian Federation, 68 Leningradskaya street, Pesochny, 197758 Saint PetersburgReferences
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