Stress hormones promote DNA damage in human oral keratinocytes

Author(s)

Vitor Bonetti Valente

• Document type: Doctoral Thesis
• Press: Araçatuba. 2020-06-02.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
• Defense date: 2020-05-29
• Advisor: Daniel Galera Bernabé; Sandra Helena Penha de Oliveira; Gisele Zoccal Mingoti

Abstract

Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well 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 than 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. 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 abolished by propranolol and glucocorticoid receptor antagonist RU486, respectively. 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. Stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis. (AU)

• FAPESP's process: 17/07784-8 - Effects of stress-related hormones on DNA damage and malignant transformation of human oral keratinocytes
• Grantee: Vitor Bonetti Valente
• Support Opportunities: Scholarships in Brazil - Doctorate