p53 gene mutational spectra in hepatocellular carcinomas induced by 2‐acetylaminofluorene and N‐nitroso‐2‐acetylaminofluorene in rats
Journal
Molecular Carcinogenesis
Journal Volume
13
Journal Issue
3
Pages
182-190
Date Issued
1995
Author(s)
Abstract
In this study, the mutation frequencies of the p53 gene in rat hepatocellular carcinomas (HCCs) induced by N?nitroso?2?acetylaminofluorene (NO?AAF) and 2?acetylaminofluorene (AAF) were 19.23% (20 of 104) and 31.1% (33 of 106), respectively. Four noteworthy features of the mutation spectrums of the p53 gene in HCCs induced by both NO?AAF and AAF were observed: (i) There was preferential clustering of mutations at exons 5–8 in both the NO?AAF or AAF groups, (ii) Nearly all the mutations (98%) induced by NO?AAF and AAF were point mutations, (iii) A high frequency of the p53 mutations were transition mutations, and the ratios of transition to transversion in the NO?AAF and the AAF group were 13:6 and 21:12, respectively. Almost all the mutations were G→A transitions and guanosine was the major target base. (iv) The frequency and base location of p53 mutations were significantly associated with cancer cell differentiation. In poorly differentiated HCCs (58 individual tumor samples), mutations were detected in 24 of 58 samples (41.1%) and clustered mostly in exons 7 and 8 (19 of 24 samples), whereas in well?differentiated HCCs (105 individual tumor samples), the incidence of mutations was low (one of 10 in the AAF group, 17 of 95 in the NO?AAF group), and the mutations were located in exon 5 (11 of 18). The biological significance of these different mutational spectra among p53 genes deserves further investigation. ? 1995 Wiley?Liss, Inc. Copyright ? 1995 Wiley?Liss, Inc., A Wiley Company
SDGs
Other Subjects
n (2 fluorenyl)acetamide; n nitroso 2 acetylaminofluorene; unclassified drug; animal cell; animal experiment; article; controlled study; gene mutation; liver carcinogenesis; liver cell carcinoma; priority journal; rat; tumor suppressor gene; 2-Acetylaminofluorene; Animal; Base Sequence; Cell Differentiation; DNA Primers; DNA, Neoplasm; Genes, p53; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Molecular Sequence Data; Nitroso Compounds; Point Mutation; Polymorphism, Single-Stranded Conformational; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't; Animalia
Type
journal article