Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile

Abstract

Background: Free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which induce oxidative and nitrative stress, are main contributors to oral carcinogenesis. The RNS (nitrosamines: nitrates, NO(3), and nitrites, NO(2)) are also produced by the reaction of ROS and other free radicals with nitric oxide (NO) and are therefore in equilibrium with it.

Methods: Whole saliva was collected from a group of 25 consenting oral squamous cell carcinoma (OSCC) patients and from a control group of 25 healthy age- and gender-matched individuals. General and specific salivary antioxidant components, salivary nitrosamines, and oxidatively damaged salivary DNA and proteins were measured.

Results: The findings showed that oxidative and nitrative stress altered the salivary composition in OSCC patients. Analyzed salivary RNS were substantially higher (NO, 60%; NO(2), 190%; NO(3), 93%), whereas all salivary antioxidants were substantially reduced. The 8-hydroxy-deoxyguanosine (8-OHdG) marker (a widely used indicator of DNA oxidation) increased by 65% and the salivary carbonylation level was significantly higher.

Conclusions: The increase in ROS and RNS may have been the event that led to the consumption and reduction of salivary antioxidant systems, thus explaining the oxidative damage to the DNA and proteins, and possibly the promotion of OSCC. The oxidized proteins and DNA found in the saliva of the cancer patients seems to be the first demonstration of a direct link between salivary free radicals, antioxidants, and OSCC. This may be important for better understanding the pathogenesis of the disease and may contribute to its diagnosis and treatment.