Stress hormones promote DNA damage in human oral keratinocytes

Author(s)

Valente, Vitor Bonetti ^[1] ; de Melo Cardoso, Diovana ^[1] ; Kayahara, Giseli Mitsuy ^{[1, 2]} ; Nunes, Giovana Barros ^[3] ; Tjioe, Kellen Cristine ^{[1, 4]} ; Biasoli, eder Ricardo ^{[1, 2]} ; Miyahara, Glauco Issamu ^{[1, 2]} ; Oliveira, Sandra Helena Penha ^[1] ; Mingoti, Gisele Zoccal ^[3] ; Bernabe, Daniel Galera ^{[1, 2]}

Affiliation

^[1] Sao Paulo State Univ Unesp, Psychoneuroimmunol Lab, Psychosomat Res Ctr, Oral Oncol Ctr, Sch Dent, 1193 Jose Bonifacio St, BR-15050015 Aracatuba, SP - Brazil

^[2] Sao Paulo State Univ Unesp, Dept Diag & Surg, Sch Dent, 1193 Jose Bonifacio St, BR-15050015 Aracatuba, SP - Brazil

^[3] Sao Paulo State Univ Unesp, Lab Reprod Physiol, Dept Anim Hlth, Sch Vet Med, 793 Clovis Pestana St, BR-16050680 Aracatuba, SP - Brazil

^[4] Sao Paulo State Univ Unesp, Lab Immunopharmacol, Dept Basic Sci, Sch Dent, 1193 Jose Bonifacio St, BR-15050015 Aracatuba, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 OCT 5 2021.
• Web of Science Citations: 0

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 gamma H2AX 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. (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
• FAPESP's process: 16/25255-0 - Effects of stress and stress-related mediators on the carcinogenesis and head neck cancer progression
• Grantee: Daniel Galera Bernabé
• Support Opportunities: Regular Research Grants