Frequent mutation of p16(CDKN2A) exon 1 during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide.
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.
Hong
Yun
Y
Department of Oral Medicine, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
Yang
Linglan
L
Li
Chunyang
C
Xia
Hongbin
H
Rhodus
Nelson L
NL
Cheng
Bin
B
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
D002273:Carcinogens; D015112:4-Nitroquinoline-1-oxide; D004247:DNA