Factors Affecting Survival in a Radiation-Induced Lymphoma Model in Mice



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Abstract

Relevance. Experimental models of total gamma irradiation at non-lethal doses are widely used to study the remote effects of radiation exposure, such as induced carcinogenesis and accelerated aging.

The aim of the study was to evaluate factors influencing lifespan and carcinogenesis parameters in mice exposed to 4-fold total gamma irradiation at a dose of 1.7 Gy weekly (total dose 6.8 Gy).

Methodology. Study was conducted in 111 male and 70 female CB6F2 mice aged 62.7±13.7 days at the beginning of radiation exposure. Body weight, time of death, and carcinogenesis parameters were assessed. In an additional group of males (n=21) irradiated on the 56-57th day of life, peripheral blood cellular composition was analyzed, and DNA comet assay was performed.

Results. Thymic lymphomas developed in 59% of males after 348.4±135.5 days and in 48% of females after 349.5±107.7 days; the average lifespan (LS) was 352.8±137.4 days in males and 349.3±115 days in females. The parameters of carcinogenesis did not depend on the age at which the first exposure was carried out. A positive relationship was found between LS and the age of the first irradiation (r=0.3020, p=0.0013 for males and r=0.3522; p<0.0001 for females), but not the initial body weight of the animals. Irradiation of mice aged 56-57 days at a dose of 1.7 Gy resulted in DNA damage marker (percentage of DNA in the comet tail) increase compared to the value before irradiation by 1.6 times after the 1st irradiation and 2.3 times after the 4th irradiation. The values of the granulocyte-lymphocyte index in the peripheral blood increased by 1.6 times after the first exposure and 2.26 times after the fourth. The values of the index obtained after the first irradiation have an inverse correlation with lifespan (r = -0.5201; p = 0.0157).

Conclusion. In the model of fractionated quadruple gamma radiation at a total dose of 6.8 Gy, two important factors associated with the lifespan were revealed: the age of the first session and the granulocyte-lymphocyte index in the peripheral blood after it. The body weight of animals at the time of the first irradiation, the level of DNA damage assessed by the DNA comet assay, and the development of lymphomas were not associated with the lifespan of animals in this model.

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About the authors

Maria N. Yurova

N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health, St. Petersburg, Russia

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 Petersburg

Alexander Leonidovich Semenov

N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

Email: genesem7@gmail.com
ORCID iD: 0000-0002-5190-0629
SPIN-code: 4301-8679

junior research fellow of laboratory of cancer chemoprevention and oncopharmacology

Elena Ivanovna Fedoros

N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

Author for correspondence.
Email: elenafedoros@gmail.com
ORCID iD: 0000-0002-2426-9843
SPIN-code: 3302-1384

Ivan Viktorovich Soloviev

N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

Email: kolonner@yandex.ru
ORCID iD: 0009-0003-0826-2101

Irina Akopovna Tumanyan

N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

Email: itumanyan@mail.ru
ORCID iD: 0000-0002-8926-1519
SPIN-code: 1165-4685

Igor Sergeevich Drachev

ФГБУ «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской Федерации

Email: dr.ingwar@mail.ru
ORCID iD: 0000-0002-1334-211X
SPIN-code: 6159-7799

Elena Andreevna Yakunchikova

ФГБУ «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской Федерации

Email: Wowmusorka@gmail.com
ORCID iD: 0000-0003-1263-744X
SPIN-code: 3557-8986

Vladimir Nikolaevich Anisimov

N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

Email: aging@mail.ru
ORCID iD: 0000-0002-3683-861X
SPIN-code: 1760-9080

член-корр. РАН, д.м.н., профессор,

Заведующий научным отделом канцерогенеза и онкогеронтологии

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