Radiomodifying properties of butylhydroxytoluene using Drosophila melanogaster as an example
Abstract and keywords
Abstract:
In experiments on Drosophila melanogaster, the radiomodifying effect of butylhydroxytoluene (BHT) was assessed by studying the level of DNA damage and lifespan in the wild-type Canton-S strain and sod-gene mutants. It was found that the introduction of BHT into the diet of Drosophila can lead to a decrease in sensitivity to chronic γ-radiation of different intensities (0.42 and 40.3 mGy/h). In individuals with normal gene functioning (Canton-S), which develop under conditions of chronic irradiation, BHT in concentrations above 1 μM has a beneficial effect on the cytogenetic index (reducing its level at dose rates of 0.42 and 40.3 mGy/h) and lifespan (increasing its parameters at dose rate of 0.42 mGy/h). A specific effect of BHT on genotypes with low activity of cytoplasmic (sod[n1]/+) and mitochondrial (sod[delta02]/+) superoxide dismutase was found. According to the "DNA damage" and "survival" parameters, the most pronounced radioprotective effect of BHT was noted in animals of the sod[n1]/+ strain. This effect was recorded at concentrations of the substance exceeding 10 μM and at all irradiation rates. In individuals of the sod[delta02]/+ strain, the antiradiation effect of BHT was revealed at concentrations of 10-20 μM (on the level of DNA damage) and 100 μM (on lifespan). The combination of BHT and chronic irradiation has a predominantly antagonistic (in all genotypes), less often synergistic/additive (in sod-mutants) character. This preparation, depending on the concentration, is able to reduce DNA damage and increase the lifespan of individuals of a certain genotype, which indicates its ability to slow down the aging process. Thus, the experimental data indicate that the introduction of BHT into the diet of Drosophila can have a radioprotective effect, adapting the organism to chronic γ-radiation. The efficiency of this effect depends on the genetic background of animals, especially on the activity level of the corresponding sod-genes.

Keywords:
Drosophila, γ-radiation, butylhydroxytoluene, DNA breaks, lifespan, antioxidant system, mutations in sod-genes
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References

1. Computational approach for determining the spectrum of DNA damage induced by ionizing radiation / H. Nikjoo, P. O’Neill, W. E. Wilson [et al.] // Radiation Research. – 2001. – Vol. 156, № 5. – P. 577–583.

2. Radiation-induced normal tissue damage: oxidative stress and epigenetic mechanisms / J. Wei, B. Wang, H. Wang [et al.] // Oxidative Medicine and Cellular Longevity. – 2019. – Vol. 4. – P. 3010342.

3. Izuchenie antioksidantnyh i radioprotektornyh svojstv izobornilfenolov pri rentgenovskom obluchenii v maloj doze [Study of antioxidant and radioprotective properties of isobornylphenols under low-dose X-ray irradiation] / L. N. Shishkina, A. Yu. Babkin, M. A. Klimovich [et al.] // Biofizika [Biophysics]. – 2019. – Vol. 64, № 6. – P. 1200–1207.

4. EFSA panel on food additives and nutrient sources added to food (ANS); Scientific opinion on the reevaluation of butylated hydroxytoluene BHT (E 321) as a food additive // EFSA Journal. – 2012. – Vol. 10, № 3. – P. 2588.

5. Thakore, K. N. Butylated hydroxytoluene / K. N. Thakore // Encyclopedia of Toxicology (Third Edition). – USA : Academic Press, 2014. – P. 583–584.

6. Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review / W. A. Yehye, N. A. Rahman, A. Ariffin [et al.] //European Journal of Medicinal Chemistry. – 2015. – Vol. 101. – P. 295–312.

7. Chapter 1.3 – Food auto-oxidation: an overview / A. Garg, R. Sharma, P. Dey [et al.] // Antioxidants Effects in Health. The Bright and the Dark Side. – Elsevier, 2022. – P. 43–68.

8. Chapter 22 – Formulation additives used in pharmaceutical products: Emphasis on regulatory perspectives and GRAS / S. Manchanda, A. Chandra, S. Bandopadhyay [et al.] // Dosage Form Design Considerations. Advances in Pharmaceutical Product Development and Research. – Academic Press, 2018. – Vol. 1. – P. 773-831.

9. Sankaranarayanan, K. The effects of butylated hydroxytoluene on radiation and chemically-induced genetic damage in Drosophila melanogaster / K. Sankaranarayanan // Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. – 1983. – Vol. 108, № 1–3. – P. 203–223.

10. Differential modifying effects of food additive butylated hydroxytoluene toward radiation and 4-nitro-quinoline 1-oxide-induced genotoxicity in yeast / K. B. Anjaria, N. N. Bhat, K. B. Shirsath [et al.] // Journal of Environmental Pathology, Toxicology and Oncology. – 2011. – Vol. 30, № 3. – P. 189–197.

11. Flybase. Revision 3. 2003. – URL: // http://flybase.bio.indiana.edu.

12. Ashburner, M. Drosophila: a laboratory handbook / M. Ashburner. – Cold Spring Harbor Laboratory Press, 1989. – 1331 p.

13. OASIS portable: user-friendly offline suite for secure survival analysis / S. K. Han, H. C. Kwon, J.-S. Yang [et al.] // Molecules and Cells. – 2024. – Vol. 47, № 2. – P. 100011. 14.

14. Influence of mus201 and mus308 mutations of Drosophila melanogaster on the genotoxicity of model chemicals in somatic cells in vivo measured with the Comet assay/ C. Bilbao, J. A. Ferreiro, M. A. Comendador [et al.] // Mutation Research. – 2002. – Vol. 503, № 1. – P. 11–19.

15. Yushkova, E. Interaction effect of mutations in the genes (piwi and aub) of the Argonaute family and hobo transposons on the integral survival parameters of Drosophila melanogaster / E. Yushkova // Biogerontology. – 2024. – Vol. 25. – P. 131–146.

16. Vliyanie kombinirovannogo dejstviya ioniziruyushchego izlucheniya i solej tyazhelyh metallov na chastotu hromosomnyh aberracij v listovoj meristeme yarovogo yachmenya [The effect of the combined action of ionizing radiation and heavy metal salts on the frequency of chromosomal aberrations in the leaf meristem of spring barley] / S. A. Geras'kin, V. G. Dikarev, A. A. Udalova [et al.] // Genetika [Genetics]. – 1996. – Vol. 32, № 2. – P. 279–288.

17. Kohn, R. R. Effect of antioxidants on lifespan of C57BL mice / R. R. Kohn // Journal of Gerontology. – 1971. – Vol. 26, № 3. – P. 378–380.

18. Effect of butylated hydroxytoluene on the mean lifespan of D. melanogaster / R. Félix, J. Ramirez, V. M. Salceda [et al.] // Drosophila Information Service. – 1970. – Vol. 45. – P. 121–123.

19. Cumming, R. B. Modification of the acute toxicity of mutagenic and carcinogenic chemicals in the mouse by prefeeding with antioxidants / R. B. Cumming, M. F. Walton // Food and Cosmetics Toxicology. – 1973. – Vol. 11. – P. 547–553.

20. Testa, B. Inhibitors of cytochrome P-450 and their mechanisms of action / B. Testa, P. Jenner // Drug Metabolism Reviews. – 1981. – Vol. 12, № 1. – P. 1–117.

21. Daniel, J. W. The metabolism of 3,5-di-tert-butyl-4-hydroxytoluene in the rat and man / J. W. Daniel, J. C. Gage, D. I. Jones // Biochemical Journal. – 1968. – Vol. 106. – P. 783–390.

22. Wieber, L. I. Urinary metabolites of 3,5-di[1)3C]-methyl-l-methyl-ethyl-4-hydroxytoluene (BHT-t3C) in man / L. I. Wieber, J. R. Mercer, A. J. Ryan // Drug Metabolism and Disposition. – 1978. – Vol. 6. – P. 296–302.

23. Petin, V. G. Kombinirovannoe vozdejstvie faktorov okruzhayushchej sredy na biologicheskie sistemy [Combined effects of environmental factors on biological systems] / V. G. Petin, B. I. Synzynys. – Obninsk : IATE, 1998. – 74 p.

24. Izuchenie gematoprotektornoj effektivnosti dikarbamina v usloviyah eksperimental'nogo postradiacionnogo kostnomozgovogo sindroma [Study on the hematoprotective effect of dicarbamine in the conditions of experimental after-radiation bone marrow syndrome] / I. Ya. Moiseeva, A. I. Zinov'ev, S. A. Nikishin [et al.] // Voprosy onkologii [Issues of Oncology]. – 2012. – Vol. 58, № 1. – P. 81–84.

25. Radiomodificiruyushchij effekt gomogenata galobakterij i ego frakcij v opytah in vitro [Radiomodifying effect of halobacteria homogenate and its fractions in vitro] / S. P. Yarmonenko, A. A. Vajnson, N. Kuhinava [et al.] // Medical Radiology and Radiation Safety. – 2010. – Vol. 55, № 6. – P. 5–7.

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