p53 gene mutational spectra in hepatocellular carcinomas induced by 2-acetylaminofluorene and N-nitro-2-acetylaminofluorene in rats

Y. S. Ho, H. T. Cheng, Y. J. Wang, J. K. Lin

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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 (on e 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.

Original languageEnglish
Pages (from-to)182-190
Number of pages9
JournalMolecular Carcinogenesis
Volume13
Issue number3
DOIs
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

2-Acetylaminofluorene
p53 Genes
Hepatocellular Carcinoma
Mutation
Exons
Mutation Rate
Neoplasms
Guanosine
Point Mutation
Cluster Analysis
N-nitroso-N(2)-fluorenylacetamide
Cell Differentiation

Keywords

  • Hepatocellular carcinoma
  • p53 gene
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

p53 gene mutational spectra in hepatocellular carcinomas induced by 2-acetylaminofluorene and N-nitro-2-acetylaminofluorene in rats. / Ho, Y. S.; Cheng, H. T.; Wang, Y. J.; Lin, J. K.

In: Molecular Carcinogenesis, Vol. 13, No. 3, 1995, p. 182-190.

Research output: Contribution to journalArticle

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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 (on e 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.",
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AB - 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 (on e 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.

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