title: ACB-PCR measurement of spontaneous and furan-induced H-ras codon 61 CAA to CTA and CAA to AAA mutation in B6C3F1 mouse liver.
abstract: Furan is a rodent liver carcinogen, but the mode of action for furan hepatocarcinogenicity is unclear. H-ras codon 61 mutations have been detected in spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors carrying H-ras codon 61 CAA to AAA mutation increased in furan-treated mice. Allele-specific competitive blocker PCR (ACB-PCR) has been used previously to quantify early, carcinogen-induced increases in tumor-associated mutations. The present pilot study investigated whether furan drives clonal expansion of pre-existing H-ras mutant cells in B6C3F1 mouse liver. H-ras codon 61 CAA to CTA and CAA to AAA mutations were measured in DNA isolated from liver tissue of female mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week for three weeks, using five mice per treatment group. Spontaneous levels of mutation were low, with two of five control mice having an H-ras codon 61 CTA or AAA mutant fraction (MF) greater than 10(-5) . Several furan-treated mice had H-ras codon 61 AAA or CTA MFs greater than those measured in control mice and lower bound estimates of induced MF were calculated. However, no statistically-significant differences were observed between treatment groups. Therefore, while sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis examined in this study (three weeks), there was not a significant expansion of H-ras mutant cells.
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, Division of Genetic and Molecular Toxicology, Jefferson, Arkansas.
authors.forename: Malathi
authors.initials: M
authors.lastname: Banda
authors.forename: Leslie
authors.initials: L
authors.lastname: Recio
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Parsons
mesh_terms: D000818:Animals; D003062:Codon / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005663:Furans / Q000633:toxicity*; D005784:Gene Amplification; D011905:Genes, ras; D008113:Liver Neoplasms / Q000235:genetics*; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009154:Mutation / Q000187:drug effects*; D016133:Polymerase Chain Reaction
chemical_list: D003062:Codon; D005663:Furans; D009153:Mutagens
keywords: B6C3F1 mouse; H-ras codon 61 mutations; furan; hepatocarcinogenesis; mode of action