EFFECT OF POLYUNSATURATED FATTY ACIDS ON THE EXPRESSION OF TRP53 IN THE DEVELOPMENT OF TONGUE TUMORIGENESIS IN MICE

DON JULIETA; FERRERO VICTORIA; MAZO TAMARA; BERNADEZ SOL; DIAZ VERÓNICA; BAROTTO NELSO N; BRUNOTTO MABEL; MARÍA EUGENIA PASQUALINI

Rosario

Congreso; LIX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2023

Oral cancers have a low survival rate and an important impact on the life quality of patients and areassociated with sociocultural health determinants such as diet. The objective was to evaluate themodulating effect of polyunsaturated fatty acids ( PUFAs) (ω-3 and ω-6) on the TRP53 expression of a tongue squamous cell carcinoma development, induced by a carcinogenic agent using murineexperimental model. The generation of this knowledge may constitute a tool that can improveprevention strategies and early diagnosis of this disease. Balb-c mice (n=72) were fed with asemisynthetic diet enriched with corn oil (Control, CM, high ω-6), or with fish oil (CP, high ω-3) or Control or Fish oil diets with DMBA (carcinogen). (Four groups were established: Control (CM)(n=12), fish control (CP) (n=12), CM + DMBA (DM)( n=24), and CP+ DMBA (DP (n=24). Tumor induction was performed by tongue topication with DMBA/formaldehyde (initiator/promoter), three times/week and at different periods: 30, 60, and 90 days. Animals were sacrificed and tongues were collected. We analyzed: histopathology (H/E stained), membrane cell lipid profile (by Gas Chromatography), DNA isolation and TRP53 codon 270 identification by PCR allele-specific. Experiments were repeated at least three times and analyzed by ANOVA, p-value<0.05 will be established for statistical significance. Higher degrees of hyperkeratosis, hyperplasia, and mitotic figures, especially in sample tongues derived from CM and CM + DMBA groups were observed in comparison to CP and CP + DMBA groups at 60 and 90 days. Cell membrane lipid profile from (CP) and ( CP+ DMBA) groups presented significantly increment in ω-3 ( EPA,20:5) at 60 days (p=0.0375) and 90 days p=0.0386); (DPA, 22:5) at 30 days (p=0.0384) and 90 days (p=0.0347) and (DHA, 22:6) at 30 days (p=0.0361) and 90 days (p= 0.0080)). The omega-6 PUFAs (LA, 18:2) and ( AA, 20:4), were increased in CM and CM + DMBA with respect to CP and CP +DMBA groups. The percentage of Trp53R270H mutated variant was higher ( 25%) in CM + DMBA in relation to the CP+DMBA (16.67%) group. The ω-3 PUFAs could prevent the DMBA mutagenic effect on the TRP53 in this tongue squamous cell carcinoma experimental model.