Dichloroacetic acid reduces Ha-ras codon 61 mutations in liver tumors from female B6C3F1 mice.
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.
Schroeder
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Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514, USA.
DeAngelo
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Mass
M J
MJ
D000818:Animals; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012737:Sex Factors
D004247:DNA; D003999:Dichloroacetic Acid