title: Frequent mutation of p16(CDKN2A) exon 1 during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide.
abstract: In this study we explored the mutation types of p16(CDKN2A) exon 1 and the corresponding frequencies in experimental rat tongue carcinogenesis. Twenty barrier Sprague-Dawley (SD) rats were divided into the control (n = 5) and experimental group (n = 15), to which 4-nitroquinoline-1-oxide (4-NQO) in drinking water was administered. Two samples of normal, three samples of moderate/severe dysplasia and four samples of invasive squamous cell carcinoma lesions were selected following strict histopathological examination in double-blind manner. The PCR products of p16(CDKN2A) exon 1 amplified from these tissues were sequenced. Point mutations of p16(CDKN2A) exon 1 were found in all of the precancerous and cancerous lesions. Half of the mutations were detected on guanine (G). Twenty mutations, including a missense mutation of the start codon resulting in alternative reading frame of p16(CDKN2A) exon 1, were also identified. These preliminary results suggested that mutation of p16(CDKN2A) exon 1 might be an early molecular event of rat tongue carcinogenesis induced by 4NQO and G was the mutation hotspot.
authors.affiliation: Department of Oral Medicine, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.forename: Linglan
authors.initials: L
authors.lastname: Yang
authors.forename: Chunyang
authors.initials: C
authors.lastname: Li
authors.forename: Hongbin
authors.initials: H
authors.lastname: Xia
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Rhodus
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004247:DNA; D005091:Exons; D019942:Genes, p16; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014062:Tongue Neoplasms / Q000139:chemically induced* / Q000235:genetics
chemical_list: D002273:Carcinogens; D015112:4-Nitroquinoline-1-oxide; D004247:DNA