Stress hormones promote DNA damage in human oral keratinocytes

Abstract Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whet...

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Autores principales:	Vitor Bonetti Valente, Diovana de Melo Cardoso, Giseli Mitsuy Kayahara, Giovana Barros Nunes, Kellen Cristine Tjioe, Éder Ricardo Biasoli, Glauco Issamu Miyahara, Sandra Helena Penha Oliveira, Gisele Zoccal Mingoti, Daniel Galera Bernabé
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b12402a76d7e411aaea6b514a1b580e9
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spelling	oai:doaj.org-article:b12402a76d7e411aaea6b514a1b580e92021-12-02T19:16:14ZStress hormones promote DNA damage in human oral keratinocytes10.1038/s41598-021-99224-w2045-2322https://doaj.org/article/b12402a76d7e411aaea6b514a1b580e92021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99224-whttps://doaj.org/toc/2045-2322Abstract Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.Vitor Bonetti ValenteDiovana de Melo CardosoGiseli Mitsuy KayaharaGiovana Barros NunesKellen Cristine TjioeÉder Ricardo BiasoliGlauco Issamu MiyaharaSandra Helena Penha OliveiraGisele Zoccal MingotiDaniel Galera BernabéNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vitor Bonetti Valente Diovana de Melo Cardoso Giseli Mitsuy Kayahara Giovana Barros Nunes Kellen Cristine Tjioe Éder Ricardo Biasoli Glauco Issamu Miyahara Sandra Helena Penha Oliveira Gisele Zoccal Mingoti Daniel Galera Bernabé Stress hormones promote DNA damage in human oral keratinocytes
description	Abstract Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.
format	article
author	Vitor Bonetti Valente Diovana de Melo Cardoso Giseli Mitsuy Kayahara Giovana Barros Nunes Kellen Cristine Tjioe Éder Ricardo Biasoli Glauco Issamu Miyahara Sandra Helena Penha Oliveira Gisele Zoccal Mingoti Daniel Galera Bernabé
author_facet	Vitor Bonetti Valente Diovana de Melo Cardoso Giseli Mitsuy Kayahara Giovana Barros Nunes Kellen Cristine Tjioe Éder Ricardo Biasoli Glauco Issamu Miyahara Sandra Helena Penha Oliveira Gisele Zoccal Mingoti Daniel Galera Bernabé
author_sort	Vitor Bonetti Valente
title	Stress hormones promote DNA damage in human oral keratinocytes
title_short	Stress hormones promote DNA damage in human oral keratinocytes
title_full	Stress hormones promote DNA damage in human oral keratinocytes
title_fullStr	Stress hormones promote DNA damage in human oral keratinocytes
title_full_unstemmed	Stress hormones promote DNA damage in human oral keratinocytes
title_sort	stress hormones promote dna damage in human oral keratinocytes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b12402a76d7e411aaea6b514a1b580e9
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Stress hormones promote DNA damage in human oral keratinocytes

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