Dichloroacetic acid reduces Ha-ras codon 61 mutations in liver tumors from female B6C3F1 mice

Schroeder, M; DeAngelo, AB; Mass, MJ

HERO ID

628909

Reference Type

Journal Article

Year

1997

Language

English

PMID

9276648

HERO ID 628909
In Press No
Year 1997
Title Dichloroacetic acid reduces Ha-ras codon 61 mutations in liver tumors from female B6C3F1 mice
Authors Schroeder, M; DeAngelo, AB; Mass, MJ
Journal Carcinogenesis
Volume 18
Issue 8
Page Numbers 1675-1678
Abstract Dichloroacetic acid (DCA), a disinfection by-product of chlorination found in drinking water, is a hepatocarcinogenic in the B6C3F1 mouse. Previous studies have shown that DCA does not significantly alter the incidence of Ha-ras codon 61 mutations in male mouse liver carcinomas from that observed in spontaneous tumors (approximately 50% have Ha-ras mutations) but it alters the proportions of mutations that occur in Ha-ras codon 61. Twenty-two tumors were produced in female B6C3F1 mice after treatment with 3.5 g DCA per liter of drinking water over a period of 104 weeks. To detect potential Ha-ras mutations in the liver tumor tissue of female B6C3F1 mice, genomic DNA was isolated from tumors that had been frozen. The polymerase chain reaction (PCR) and single-stranded conformational polymorphism (SSCP) was used to screen tumor DNA for mutations in Ha-ras exon 2. In DNA from liver tumors in female B6C3F1 mice induced by DCA-treatment we found only one mutation in exon 2 among the 22 tumors analyzed (4.5%). Direct-sequencing of exon 2 revealed a CAA to CTA transversion in Ha-ras codon 61. The result of this study indicates that tumor formation in DCA-treated female B6C3F1 mice is, therefore, not associated with a mutationally activated Ha-ras codon 61. This result differs from previous results obtained in male B6C3F1 mice.
Doi 10.1093/carcin/18.8.1675
Pmid 9276648
Wosid WOS:A1997XQ87800036
Url http://carcin.oxfordjournals.org/cgi/reprint/18/8/1675
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Language Text English
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