title: Ras gene mutation is not related to tumour invasion during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.
abstract: BACKGROUND
  The aim of this study was to investigate whether mutations in the genes H-ras and K-ras were related to the mechanism of invasion as a result of the immunoexpression of H-Ras, Ki-67, alpha-smooth muscle actin (SMA) and vascular endothelial growth factor (VEGF) during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis.
  
  
  METHODS
  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 and 20 weeks. Ten animals were used as negative control.
  
  
  RESULTS
  Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, Ki-67 was overexpresssed in the 'normal' oral epithelium. In pre-neoplastic lesions at 12 weeks following carcinogen exposure, the levels of Ki-67 were increased (P < 0.05) when compared to negative control. Ki-67, alpha-SMA and VEGF were also overexpressed in squamous cell carcinomas induced after 20 weeks of treatment with 4NQO. No significant statistical differences (P > 0.05) were found in H-ras protein expression for all experimental periods evaluated that corresponded to normal oral mucosa, hyperplasia, dysplasia and squamous cell carcinomas. In the same way, no mutations in H-ras or K-ras genes were found.
  
  
  CONCLUSIONS
  Our results support the idea that expression of Ki-67 plays a crucial role during malignant transformation being closely related to neoplastic conversion of the oral mucosa cells. However, it seems that mutations in the ras genes are not involved to experimental tongue carcinogenesis induced by 4NQO.
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, UNIFESP, SP, Brazil.
authors.forename: Ana C C
authors.initials: AC
authors.lastname: Fracalossi
authors.forename: Larissa
authors.initials: L
authors.lastname: Comparini
authors.forename: Karina
authors.initials: K
authors.lastname: Funabashi
authors.forename: Carla
authors.initials: C
authors.lastname: Godoy
authors.forename: Edna S M
authors.initials: ES
authors.lastname: Iwamura
authors.forename: Fábio D
authors.initials: FD
authors.lastname: Nascimento
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.forename: Celina T F
authors.initials: CT
authors.lastname: Oshima
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ribeiro
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D018631:ras Proteins / Q000096:biosynthesis
chemical_list: D000199:Actins; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D015112:4-Nitroquinoline-1-oxide; D018631:ras Proteins