Imbalance of tumor suppression genes expression following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.
This study was undertaken to investigate, by immunohistochemistry, the expression of some tumor suppressor genes such as p16, p21 and Retinoblastoma (Rb) during 4-Nitroquinoline 1-oxide induced rat tongue carcinogenesis. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Neither histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, nor statistically significant differences (p>0.05) in expression of all the tumor suppressor genes were found when compared to the negative control. However, the levels of Rb were increased (p<0.05) in pre-neoplastic lesions at 12 weeks following carcinogen exposure. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, p16 and Rb were expressed in some tumor cells. Taken together, the results support the belief that the expression of Rb is closely event-related to malignant transformation and conversion of the oral mucosa, being a reliable biomarker linked to oral cancer pathogenesis.
Ribeiro
Daniel Araki
DA
Department of Pathology, Federal University of Sao Paulo, Brazil. daribeiro@unifesp.br
Fracalossi
Ana Carolina Cuzzuol
AC
Uatari
Silvia Akemi
SA
Oshima
Celina Tizuko Fujiyama
CT
Salvadori
Daisy Maria Favero
DM
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016161:Genes, Retinoblastoma / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects* / Q000502:physiology; D019942:Genes, p16 / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D002273:Carcinogens; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; D015112:4-Nitroquinoline-1-oxide