title: Systemic toxic effects during early phases of topical 4-NQO-induced oral carcinogenesis in rats.
abstract: BACKGROUND
  Most studies have demonstrated 4-NQO toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4-NQO topical application during early phases of oral cancer induction.
  
  
  METHODS
  A 4-NQO propylene glycol ointment was topically applied on the rat tongue three times a week for 16 weeks. Local and systemic 4-NQO toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (PCNA) immunohistochemistry.
  
  
  RESULTS
  Significant reduction in body weight gain and in white blood cell count as well as significant increase in serum ALT and AST was observed after 16 weeks of 4-NQO topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected.
  
  
  CONCLUSIONS
  4-NQO topical application on the tongue of rats for 16 weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.
authors.affiliation: General Pathology Department, School of Dentistry, University of SãoPaulo, São Paulo, Brazil.
authors.forename: Ana Rita Ribeiro
authors.initials: AR
authors.lastname: Barcessat
authors.forename: Isaac
authors.initials: I
authors.lastname: Huang
authors.forename: Gustavo Davi
authors.initials: GD
authors.lastname: Rabelo
authors.forename: Flávia Cristina Perillo
authors.initials: FC
authors.lastname: Rosin
authors.forename: Luciana Gonçalves Valente
authors.initials: LG
authors.lastname: Ferreira
authors.forename: João Gualberto
authors.initials: JG
authors.lastname: de Cerqueira Luz
authors.forename: Luciana
authors.initials: L
authors.lastname: Corrêa
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000287:Administration, Topical; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001774:Blood Chemical Analysis; D063646:Carcinogenesis / Q000139:chemically induced*; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D015603:Keratinocytes / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects; D007958:Leukocyte Count; D007972:Leukoplakia, Oral / Q000139:chemically induced; D008099:Liver / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects; D015363:Quinolones / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects; D014059:Tongue / Q000187:drug effects; D014062:Tongue Neoplasms / Q000139:chemically induced; D015430:Weight Gain / Q000187:drug effects
chemical_list: C120195:4-nitroquinolone-1-oxide; D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D015363:Quinolones; D012709:Serum Albumin; D015112:4-Nitroquinoline-1-oxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: 4-NQO toxicity; carcinogenesis model; potentially malignant oral lesions