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N-acetoxy-N-acetyl-2-aminofluorene-induced mutation spectrum in a human hprt cDNA shuttle vector integrated into mammalian cells.

Abstract：

:The spectrum of mutations induced by N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) was examined by the pZipHprtNeo shuttle vector in mammalian cells. The vector carries a cDNA of the human hypoxanthine phosphoribosyl transferase (hprt) gene, which is stably integrated into chromosomal DNA of a mouse cell line, VH12. After treatment of the cell with N-AcO-AAF, 48 independent 6-thioguanine-resistant clones were obtained and altered sequences of the mutated cDNA hprt genes were determined. Frameshifts and deletions were the predominant mutational events (68%) induced by N-AcO-AAF and the remainder were base substitutions (32%) of various types. Analysis of sequence alterations at all the sites of mutation revealed that: (i) > 65% of mutations occurred at G:C sites, suggesting C8G adducts are responsible premutagenic lesions for these mutations; and (ii) short sequence repeats were frequently found at the sites of frameshift and deletion, and slippage--misalignment is the suggested mechanism for the induction of mutations at these sites. Implied significance of slippage--misalignment as a fundamental mechanism for mutagenesis is discussed.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Ogawa HI,Kimura H,Koya M,Higuchi H,Kato T

doi

10.1093/carcin/14.11.2245

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

2245-50

issue

11

eissn

0143-3334

issn

1460-2180

journal_volume

14

pub_type

杂志文章

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