Investigating the safety of photobiomodulation in oral carcinogenesis: insights into cell proliferation, invasion, and apoptosis via the 4NQO model

Sep 21, 2026

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Assessment of photobiomodulation (PBM) safety in oral carcinogenesis induced by 4NQO evaluated cell proliferation and apoptosis. Wistar rats received systemic 4NQO for 12 (n=33) or 20 weeks (n=33) and were assigned to Control, PBM 0.3 J, or PBM 1 J, with PBM delivered three times weekly. Animals were euthanized at weeks 12 and 20, and anti-ROS1 and anti-p53 immunoreactivity was quantified. Nodular lesions at 12 weeks differed in PBM 1 J (p=0.005). Histopathology showed no significant group differences (12 weeks p=0.30; 20 weeks p=0.58). PBM did not alter lesion progression or proliferative/apoptosis protein expression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background and rationale

Multistep process of oral carcinogenesis

Photobiomodulation mechanisms and clinical indications

Study design

4NQO-induced oral carcinogenesis model

PBM dosing groups and administration schedule

Euthanasia and immunoreactivity assessment

Statistical analysis

Results

Lesion development at 12 and 20 weeks

Histopathological characteristics

Immunostaining of p53 and ROS1

Correlation with clinicopathological data

Conclusions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Investigating the safety of photobiomodulation in oral carcinogenesis: insights into cell proliferation, invasion, and apoptosis via the 4NQO model Lauren Frenzel Schuch1,2, Daniela Campagnol3, Tuany Rafaeli Schmidt4, Carolina Horn Troian Michel5, Tuane Nerissa Alves Garcez3, Vanessa Rodrigues Velho4, Vivian Petersen Wagner6, Rogerio Moraes Castilho7, Felipe Martins Silveira2, Ronell Bologna-Molina2, Marco Antonio Trevizani Martins4,8, Chris Krebs Danilevicz9, Alan Roger Santos-Silva1, Pablo Agustin Vargas1 & Manoela Domingues Martins1,4,8􀀍 The present investigation aimed to assess the safety of photobiomodulation (PBM) on the oral carcinogenesis process induced by 4NQO, focusing on cell proliferation and apoptosis. Sixty-six Wistar rats received systemic 4NQO for 12 (n = 33) and 20 weeks (n = 33), divided into Control group, PBM 0.3 J, and PBM 1 J. Applications for PBM occurred three times a week. At weeks 12 and 20, the animals were euthanized. The immunoreactivity for anti-ROS1 and anti-p53 antibodies was also assessed. Statistical analysis was assessed by multiple t-tests, Kruskal-Wallis, and Spearman’s correlation. At 12 weeks, PBM 1 J group had nodular lesions, distinct from control and PBM 0.3 J groups (p = 0.005) . At 20 weeks, nodular lesions were common in control and PBM 0.3 J groups. Histopathological characteristics did not significantly differ between groups at 12 (p = 0.30) and 20 weeks (p = 0.58) . Epithelial dysplasia (n = 21) was common at 12 weeks. After 20 weeks, most of the cases revealed squamous cell carcinoma (n = 24). No differences were observed in the immunostaining of p53 and ROS1 among the control and experimental groups and there was no correlation of these proteins with clinicopathological data. During the carcinogenesis process, the PBM did not modify the development of oral lesions and the expression of proliferative and apoptosis proteins. Keywords Oral cancer, Oral potentially malignant disorder, Carcinogenesis, Leukoplakia, Photobiomodulation therapy, Laser therapy Oral carcinogenesis is a multifactorial process where mutations build up over time until a malignant tumor is developed1. Neoplastic cells differ from normal cells in a variety of ways, including resistance to anti-growth signals, evasion of apoptosis, self-sufficiency in growth signals, limitless potential for replication, encouragement ofangiogenesis, capacity for tissue invasion and metastasis, altered metabolic pathways, and immunity evasion2,3. These features can enable cancerous cells to endure, multiply, and disseminate outside of their original site. The high death rate, destructive nature of conventional treatments, frequent comorbidities, and frequent oral 1Oral Diagnosis Departament, Piracicaba Dental School, Universidade Estadual de Campinas, Piracicaba, São Paulo, Brazil. 2Department of Diagnosis in Pathology and Oral Medicine, Molecular Pathology area, School of Dentistry, Universidad de la República, Montevideo, Uruguay. 3Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. 4Departament of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. 5Departament of Edodontics, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. 6Department of Dentistry, School of Dentistry, Universidade de São Paulo (FOUSP), São Paulo, Brazil. 7School of Dentistry, Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI, USA. 8Department of Oral Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. 9Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. 􀀍 email: [manomartins@gmail.com](manomartins@gmail.com) [www. nat

FAQs

What was the aim of this investigation?

To assess the safety of photobiomodulation (PBM) during 4NQO-induced oral carcinogenesis, focusing on cell proliferation and apoptosis outcomes.

How were the rats treated and when were they evaluated?

Sixty-six Wistar rats received systemic 4NQO for 12 or 20 weeks, then were assigned to Control, PBM 0.3 J, or PBM 1 J, with PBM applied three times per week. Animals were euthanized at weeks 12 and 20.

Did PBM alter lesion progression and the expression of key proteins?

PBM did not modify the development of oral lesions or the expression of proliferative and apoptosis proteins, and no differences were observed in p53 and ROS1 immunostaining between groups.

Were p53 and ROS1 associated with clinicopathological data?

No correlation was observed between p53 and ROS1 with clinicopathological data across the control and experimental groups.

Sep 21, 2026

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