title: Alkylation-induced genotoxicity as a predictor of DNA repair deficiency following experimental oral carcinogenesis.
abstract: The aim of this study was to evaluate alkylation induced genotoxicity as a result of DNA repair deficiency during 4-nitroquinoline 1-oxide (4NQO)-induced rat tonguecarcinogenesis by means of single cell gel (comet)assay. 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. Blood samples and oral mucosa cells collected from all animals were divided into two aliquots of 20 lL each to study basal DNA damage and DNA damage due to genotoxin sensitivity.The first aliquot was processed immediately for comet assay to assess basal DNA damage. The second aliquot was treated with a known genotoxin, methylmetanesulfonate.Significantly greater DNA damage was noticed to oral mucosa cells from 4, and 12 weeks posttreatment.Peripheral blood cells did show statistically significant differences (P\0.05) after 20 weeks-group(squamous cell carcinoma). In conclusion, alkylation induced genotoxicity as a result of DNA repair deficiency is present in oral mucosa cells following oral experimental carcinogenesis.
authors.affiliation: Department of Biosciences, Federal University of São Paulo UNIFESP, Av. Ana Costa, 95, Vila Mathias, Santos, SP, Brazil.
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Carvalho
authors.forename: Juliana
authors.initials: J
authors.lastname: Noguti
authors.forename: Victor Hugo P
authors.initials: VH
authors.lastname: da Silva
authors.forename: Rogério A
authors.initials: RA
authors.lastname: Dedivitis
authors.forename: Marcello
authors.initials: M
authors.lastname: Franco
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ribeiro
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000284:Administration, Oral; D000478:Alkylation; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D020552:Comet Assay; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D060766:Drinking Water; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D060766:Drinking Water; D015112:4-Nitroquinoline-1-oxide; D004247:DNA; D008741:Methyl Methanesulfonate