Abstract
Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.
Highlights
Animals and experimental conditionsAll experiments with animals followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Welfare Committee at the São Paulo State University (UNESP), School of Dentistry, Aracatuba, São Paulo
We investigated the effects of social isolation on the oral squamous cell carcinoma (OSCC) occurrence in male Wistar rats underwent chemically induced carcinogenesis
Three rats from control group and two rats from isolated group were sensitive to the toxic effects of 4-nitroquinoline 1-oxide (4NQO) treatment and died during the first month of oral carcinogenesis
Summary
All experiments with animals followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Welfare Committee at the São Paulo State University (UNESP), School of Dentistry, Aracatuba, São Paulo. Sixty-two male Wistar rats were obtained from the Central Animal Care Facility of the university and housed in ventilated cages, which were placed in an environment room with controlled temperature (25±2 ̊C), humidity (55±5%) and light (12-h light/dark cycle). The animals had ad libitum access to drinking water and standard pellet diet (Purina, Paulınia, SP, Brazil) throughout out the experimental period
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